Showing papers in "Pflügers Archiv: European Journal of Physiology in 1979"

The steady-state TTX-sensitive ("window") sodium current in cardiac Purkinje fibres

Abstract: Voltage clamp experiments on isolated sheep Purkinje fibres showed an increase of the steady state outward membrane current, over the potential range -65mV to -15 mV, in the presence of tetrodotoxin (TTX, 3.10(-5 M). This "window" current is considered to be the steady state component of the fast sodium current (INa), resulting from the crossover of the activation and inactivation curves which govern the opening of the sodium channel. TTX had no significant effect on the reversal potential, activation curve, kinetics or instantaneous I-V relationship of the pacemaker current IK2. The window found in these experiments extends to potentials well into the range of the action potential plateau. Consequently small changes of the steady state INa might have large effects on the action potential duration. The effects of TTX and local anaesthetics are discussed in this context.

Decrease of calcium binding by the red blood cell membrane in spontaneously hypertensive rats and in essential hypertension.

Abstract: Ca binding in the red blood cell (RBC) membrane of spontaneously hypertensive rats (SHR) and of patients with essential hypertension was studied. Under conditions of physiological concentration of free Ca in the incubation medium of RBC the outer part of the membrane binds 393±32 and 435±30 nmole of Ca per ml of RBC in rats and humans, respectively, without essential differences in the amount of Ca in hypertensive individuals as compared to the normotensive controls.

A micropuncture study of the renal handling of lithium.

Abstract: Although clearance studies in man and experimental animals indicate that filtered lithium is reabsorbed primarily in the proximal tubule, it is unclear whether lithium is also reabsorbed in distal portions of the nephron. Micropuncture studies were, therefore, performed to determine the nephron sites involved in lithium transport during free flow. A method was established to estimate the concentration of lithium in nanoliter samples, using the Helium Glow photometer, which permitted the accurate measurement of lithium in tubular fluid samples over a range from 0.5–30.0 mM. Approximately 56% of filtered lithium and tubular fluid was reabsorbed at the end of the proximal convolution, while at the early distal tubule 75% of filtered lithium and water was reabsorbed. There was no change in net transepithelial movement of lithium beyond the loop of Henle. These data suggest that lithium transport is localized to the proximal tubule, including the pars recta. Lithium reabsorption does not occur in distal tubule or collecting duct. Beyond the early distal tubule net movement of lithium and sodium is dissociated.

Effect of organic acid absorption on bicarbonate transport in rat colon.

Abstract: The absorption of organic anions and the influence of these anions on the movement of HCO 3 − were studied in vivo in rat colon using a perfusion technique. The absorption of short chain fatty acids (SCFA's) such as acetate, propionate, and butyrate was much greater than that of succinate or lactate. With increasing initial concentration of SCFA up to 100 mmol · l−1, SCFA absorption increased linearly in correspondence with HCO 3 − appearance. FinalpCO2 level of the perfusion solution with SCFA was the same as the plasma level. Among the SCFA's, no significant differences in absorption or their effects on HCO 3 − appearance were observed. The presence of Na+ stimulated SCFA absorption, and the maximum value was obtained at more than 100 mmol · l−1 of Na+. These results suggest that a specific system for HCO 3 − secretion activated by SCFA exists in the colon, and that this system may control the intraluminal pH by the alkalization of intestinal contents.

Measurements of the perivascular PO2 in the vicinity of the pial vessels of the cat.

Abstract: \(P_{O_2 } \) 's in the environment of the pial microvessels of the cat were measured using recessed tip oxygen microelectrodes. Measurements were made on the surface of vessels with internal diameters ranging from 200μm to 22μm. Blood oxygen partial pressures were also measured inside these vessels by penetrating the vessels with sharpened electrodes. Both intravascular and extravascular\(P_{O_2 } \) values decreased progressively from the large arterial vessels down to the small arterioles. The observed values of intravascular\(P_{O_2 } \) showed a systematic longitudinal decrease from 98.5±10.7 (SEM) mm Hg in the largest vessels down to 72.6±3.6 mm Hg in the smallest vessels. In addition to the longitudinal gradient, a transmural gradient was observed across the walls of the microvessels. The difference between blood\(P_{O_2 } \) and vessel surface\(P_{O_2 } \) was 27.0±2.5 mm Hg in the largest vessels and 6.0±2.2 in the smallest. The mean wall thickness in these groups of vesseis were 27.0±1.5 and 7.5±0.8 μm respectively. Measurements of the minimum tissue\(P_{O_2 } \) on the exposed surface of the cortex yielded a value of 25.4±6.6 mm Hg. Systemic arterial partial pressure of oxygen averaged 94.7±4.7 mm Hg. The data indicate that significant gradients for oxygen exist both longitudinally and radially in association with the pial vessels. The longitudinal gradients represent losses of oxygen from the precapillary vessels. The transmural gradients are apparently the result of both consumption by the microvessel wall and diffusional gradients due to oxygen flux into the extravascular space.

Thermoregulation in the diabetic-obese (db/db) mouse. The role of non-shivering thermogenesis in energy balance.

Abstract: 1 Thermoregulation and non-shivering thermogenesis have been studied in the genetically diabetic obese (db/db) mouse 2 At all environmental temperatures between 33 and 10 degrees C the body temperature of the diabetic mice was lower than that of the normal littermates, the difference varying from 11 degrees C at 33 degrees C to 45 degrees C at 10 degrees C 3 At 4 degrees C the diabetic mice rapidly died (32h) of hypothermia while the normal mice maintained their body temperature within the normal range 4 At 23 degrees C the diabetic animals exhibited a diurnal rhythm in body temperature which was similar in both phase and amplitude to the controls, but at every point throughout the 24h cycle the temperature of the mutants was lower by 1--2 degrees C 5 The resting metabolic rate at thermoneutrality (33 degrees C) was higher per whole animal for the diabetics than for the normals However, at temperatures below thermoneutrality the converse was observed; between 30 and 4 degrees C the RMR of the mutants was lower than the controls by approximately 25% 6 The capacity for non-shivering thermogenesis in diabetic mice was only one-half that found in normal animals 7 The diabetic mouse has abnormalities in thermoregulation and non-shivering thermogenesis which are similar to those found in the genetically obese (ob/ob) mouse It is concluded that the high metabolic efficiency of the diabetic mouse, like that of the ob/ob mouse, can be explained by a reduced energy expenditure on thermoregulatory thermogenesis; this may represent a primary mechanism for the operation of the "thirfty genotype" associated with obesity and diabetes

Simultaneous measurements of microflow and evoked potentials in the somatomotor cortex of the cat brain during specific sensory activation

Abstract: The behaviour of both microflow and evoked potentials was investigated in the right somatomotor cortex of the cat (anaesthetized with chloralose) during electrical stimulation of the contralateral left forepaw. Frequency, amplitude, and time of stimulation were varied. Using the local hydrogen clearance method the changes of microflow were continuously monitored in the same cortical area from which the evoked potentials were recorded.

A cholinergic mechanism involved in the respiratory chemosensitivity of the medulla oblongata in the cat.

Abstract: 1. Cholinomimetic and adrenomimetic substances were tested on the chemosensitive zones of the ventral surface of the medulla oblongata using a plexiglas ring method. Tidal volume and respiratory frequency, arterial pressure and heart frequency were observed. 2. The increase of ventilation and the depression of arterial blood pressure by locally applied acetylcholine could be blocked by previous local application of atropine. It is therefore assumed that the acetylcholine receptors have muscarinic properties. 3. Nicotine in a small dose raises arterial pressure and with higher doses a drop is observed. The responses of respiration and of arterial pressure to nicotine were blocked by previous intravenous administration of hexamethonium. 4. Local application of atropine in the caudal (L) and rostral (M) chemosensitive zones reduced resting ventilation and the slope of the ventilatory response to CO2-inhalation. Physostigmine in these areas enhanced resting ventilation leaving unchanged the slope of the ventilatory response to CO2-inhalation. 5. With high concentrations of (L)-noradrenaline and (L)-adrenaline a slight increase of arterial pressure was seen while serotonin caused a drop. 6. These results together with those of Fukuda and Loeschcke (1978) suggest that a cholinergic transmission in the surface layer of the ventral medulla is a component in the respiratory and circulatory control systems.

Elimination of central chemosensitivity by coagulation of a bilateral area on the ventral medullary surface in awake cats

Abstract: Breathing and respiratory response to CO2 were observed in 6 awake cats and 1 control before and after bilateral coagulation of the formerly described area S (Schlafke and Loeschcke, 1967) on the ventral medullary surface under hyperoxic conditions. Ventilation decreased,PCO2 rose and CO2 response was almost or completely abolished in 4 cats, and moderately reduced in 2 cats. Inhalation of CO2 had an inhibitory effect on ventilation in two cases. In some instances the respiratory frequency was increased by CO2. Periodic breathing as well as spotaneous hyperventilatron elicited by ‘arousal’ indicate parallels to the Pickwickian or Ondine's curse syndrome. No respiratory changes were produced by a lesion on the pyramidal tract medial to the area S. It is concluded that central chemosensitivity can be eliminated within the superficial layer of the area S. The loss of CO2 response seems to be correlated with complete destruction of the superficial nerve cells located within the area S (Petrovický, 1968) and degeneration within the ventral part of the nucleus paragigantocellularis.

Studies on the synaptic interconnection between bulbar respiratory neurones of cats.

Abstract: In cats anaesthetized with pentobarbital, medullary respiratory neurones of both dorsal and ventral populations were recorded intracellularly with 1 mol·l−1 KCl-electrodes. The neurones were classified according to the projection of their axons to the spinal cord (bulbospinal neurones) or to the vagal nerves (vagal neurones). Those neurones which could not be activated antidromically (NAA-neurones) by either procedure were subdivided into (inspiratory) Rβ-neurones, which were monosynaptically excited by lung stretch receptor afferents, and into inspiratory and expiratory NAA-neurones, which did not receive a direct synaptic input, from these afferents. All types of neurone investigated revealed postsynaptic activity during both inspiration and expiration. The periods when synaptic activity was minimal were the periods of transition between respiratory phases. The input resistance of most respiratory neurones varied in parallel with the respiratory cycle. A drastic fall of the input resistance during expiration was observed in Rβ-neurones and in some inspiratory vagal neurones. This was not seen in inspiratory bulbospinal neurones. In stable intracellular recordings, periodic postsynaptic inhibition was demonstrated in 52 of 53 respiratory neurones by IPSP reversal following chloride injection. Maximal membrane potential then was generally reached during one of the periods of respiratory phase transition. Reasons for the failure of others to demonstrate these IPSPs are presented and discrepancies between other findings and these are discussed. It is concluded that reciprocal inhibition between bulbar respiratory neurones does exist and is a general phenomenon. It is argued that reciprocal inhibition is the fundamental mechanism underlying respiratory gating of afferent inputs. The probable existence of recurrent inhibition is inferred from the changes in the pattern of membrane depolarization during the active period of neurones.

Changes in the capillarity of skeletal muscle in the growing rat.

Abstract: Capillary density (CD), capillary to fiber ratio (C/F), fiber cross sectional area (FCSA) and fiber composition were measured in the soleus and the gastrocnemius (medial head) muscles of rats weighing between 99 and 666 g. Muscle samples obtained from the anesthetized animal were rapidly frozen (−130°C) sliced transversely at 16–18 μm, and treated histochemically by the ATPase method after preincubation at pH's of 4.0 and 4.4 to visualize capillaries and typify fibers. In both muscles the FCSA was positively related to body weight (BW) and muscle weight. At a given BW, the FCSA of the soleus was greater than that of the gastrocnemius. In both muscles CD decreased hyperbolically with FCSA (soleus: CD=1.0613 ×106/FCSA+298.71; gastrocnemius: CD=1.0349 ×106/FCSA+240.74). At the same time a positive linear correlation between C/F and FCSA was found (soleus: C/F=3.92×10−4 FCSA+0.82; gastrocnemius: C/F=2.90×10−4 FCSA+0.93). At a given FCSA, CD and C/F were greater in the soleus than in the gastrocnemius because of differences in fiber composition between the two muscles. The soleus had only oxidative fibers (STO and FTOG) whereas the gastrocnemius had 54% glycolytic fibers (FTG). The very large variability in CD and C/F values reported in the literature could, in part, be due to the differences in capillarity observed with maturation. A change in fiber composition with BW was observed in the soleus, but no systematic change occurred in the gastrocnemius.

Presynaptic excitability changes induced by morphine in single cutaneous afferent C- and A-fibers.

Abstract: Intraspinal microstimulation was used to test the excitability of single cutaneous (sural) A- and C-fibers at their central terminals in the cat. Systemic morphine (1.0–2.6 mg/kg) increased the antidromic threshold to 110% (mean value) of control in C-fibers. In some of the C-fibers this effect was reversed by naloxone. A-fibers were not consistently affected by mophine.

A cholinergic mechanism involved in the neuronal excitation by H+ in the respiratory chemosensitive structures of the ventral medulla oblongata of rats in vitro.

Abstract: The mechanism of neuronal excitation by H+ in the medullary chemosensitive structures was analyzed in brains slices of the rat in vitro. Responses of neurons to H+ in the ventral surface layer were compared with responses to various transmitter substances. Neurons excited by H+ were always also excited by acetylcholine (ACh). ACh increased the activity of 70% of superficial ventral medullary neurons. Effects of noradrenaline and serotonin on the activity of neurons were largely opposite to that of H+. Cholinergic blocking agents like atropine, hexamethonium and mecamylamine depressed the H+-elicited excitation of neurons. The cholinesterase inhibitor, eserine, increased the neuronal activity. In the presence of eserine, a solution of low pH caused further increase in discharge of most neurons. The low pH solution prolonged and augmented the excitatory action of ACh on the ventral medullary neurons.

Kinetics and magnitude of the time-dependent potassium current in the rabbit sinoatrial node: effect of external potassium.

Abstract: The properties of the time-dependent potassium current in the sinoatrial node of the rabbit heart were investigated. The following results were obtained: The present observations on the potassium currenti K agree with those obtained for similar current systems in other cardiac tissues. An important new finding is that the kinetics and the maximum conductance ofi K show a remarkable insensitivity to changes in the external K concentration.

Phosphate transport by rat renal brush border membrane vesicles: influence of dietary phosphate, thyroparathyroidectomy, and 1,25-dihydroxyvitamin d3

Abstract: In the present work we have investigated whether the changes in the renal handling of inorganic phosphate (Pi) induced by 1) dietary Pi, 2) removal of parathyroid glands and 3) 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], are associated with alterations in the Na-dependent Pi uptake by brush border membrane vesicles (BBMV) isolated from renal cortex. Shamoperated (SHAM) or thyroparathyroidectomized (TPTX) rats treated or not with 26 pmol/day of 1,25 (OH)2D3i.p. were fed low (0.2%) or high (1.2%)P diet for 7 days. The results showed that in SHAM, TPTX and TPTX+1,25 (OH)2D3 the Pi uptake by BBMV was greater after low than high Pi diet. It was greater in TPTX than in SHAM counterparts fed either diets. In TPTX fed low or high Pi diet 1,25 (OH)2D3 decreased the Pi uptake to the level observed in SHAM. A striking parallelism was found between variations in Pi uptake by BBMV and in the tubular Pi reabsorption of the whole kidney. The Na-dependent glucose, the mannitol uptake by BBMV, and the alkaline phosphatase activity in cortical homogenates and BBMV were not affected by the various treatments. Thus, dietary Pi, chronic TPTX and 1,25 (OH)2D3 appear to specifically affect the Na-dependent Pi transport system bound to the brush border membranes of renal cortical tubules. The alterations observed at this membrane level could account, at least in part, for the changes induced by these three factors on the overall tubular reabsorption of Pi.

Responses of Purkinje cells of the cerebellar vermis to neck and macular vestibular inputs.

Abstract: 1. The dynamic analysis of the control exerted by neck and macular vestibular receptors on the cerebellar cortex has been investigated in precollicular decerebrate cats submitted to sinusoidal rotation along the longitudinal axis of the animal at the frequency of 0.026 Hz and at peak amplitudes up to 10° for the neck input and 15° for the macular input. 2. Purkinje (P) cells located in the vermal cortex of the cerebellar anterior lobe, particularly in the longitudinal parasagittal zone which projects to the ipsilateral lateral vestibular nucleus (LVN), showed a sinusoidal modulation of the firing rate in response to sinusoidal stimulation of the neck receptors or the vestibular receptors, the phase of the responses being in most units related to the extreme neck or head position. Mossy fiber (MF) and/or climbing fiber (CF) responses of the same or different P-cells to the two inputs were observed. 3. The sensitivity of the MF-response of the P-cells to the neck input, elicited by sinusoidal rotation of the neck and expressed in per cent of the average firing rate per degree of neck rotation, corresponded on the average to 2.71±1.67, S. D. This value was significantly higher than that of the MF-response of the P-cells to the macular input elicited by sinusoidal tilt along the longitudinal axis of the whole animal, which corresponded to 1.71±1.01, S.D. 4. Most of the MF-responses of the P-cells to the neck input were characterized by an excitation during side-down rotation of the neck and by an inhibition during side-up rotation, whereas most of the MF-responses of the P-cells to the macular input showed just the opposite behavior, being inhibited by side-down tilt of the animal and excited by side-up tilt. 5. Units which received a convergent input from both neck and macular receptors and showed an antagonistic pattern of response to the two inputs were tested during rotation of the head alone, in order to excite simultaneously the two kinds of receptors. Due to the higher sensitivity of the neck over the macular response, the magnitude of the combined response tended to be similar to the difference between the individual ones. Moreover, the phase of the resulting response was always modified with respect to that of the response to the neck input alone, and became in some instances related to velocity of neck rotation rather than to neck position. 6. These findings indicate that opposite responses to neck and macular inputs occur at corticocerebellar level. However, a final integration of the two inputs, leading to suppression of the conflicting responses, may occur either at medullary (LVN) or at spinal cord level.

Topography of the respiratory and circulatory responses to acetylcholine and nicotine on the ventral surface of the medulla oblongata.

Abstract: 1. Acetylcholine and nicotine were superfused on the ventral medullary surface between the ponto-medullary border and C1 in anaesthetized cats in order to determine the topical distribution of their actions on respiration and circulation. 2. Acetylcholine (10−4 g·ml−1=5.5·10−4 mMol·ml−1) produced an increase in respiration and a lowering of blood pressure. The magnitude and the time course of the responses varied according to the points of superfusion on the surface. 3. Nicotine (10−4 g·ml−1=6.2·10−4 mMol·ml−1) elicited hyperventilation and more often an increase in arterial pressure on unilateral superfusion of the surface. In some cases, however, a drop in blood pressure was also observed. 4. The responsive regions of the surface on which nicotine acted and elicited hyperventilation, bear a close resemblance to the regions responsive to acetylcholine. 5. The topographical distribution of the respiratory effects elicited by the above-mentioned drugs were similar to the distribution of the responses to changes in pH on the ventral medullary surface or to electrical stimulation. 6. Procaine (2·10−2 g·ml−1=7.3·10−2 mMol·ml−1) applied bilaterally in the intermediate zone (S) caused profound inhibition of respiration and of arterial profound inhibition of respiration and of arterial pressure. Procaine at this concentration also inhibited respiratory hyperventilation caused by nicotine (10−4 g·ml−1=6.2·10−4 mMol·ml−1) applied to the caudal and rostral areas.

The cholinergic pathway to cerebral blood vessels. II. Physiological studies.

Abstract: The effect of stimulating the greater superficial petrosal nerve (g.s.p.n.) upon retroglenoid venous blood flow has been tested in anaesthetized, paralysed and artificially ventilated rats. In 11 out of 15 tests, blood flow increased by an average of 25% with a time to peak response of 28 s. This response was abolished with the injection of atropine 0.1 mg kg−1 injected intra-arterially. With both petrosal nerves intact, the administration of 6–7% CO2 in air or 15% O2 in N2 caused average increases in blood flow of 105% and 45% respectively. These responses were not affected by bilateral section of the g.s.p.n. Similar experiments were carried out in 5 anaesthetized, spontaneously breathing rabbits in which, in addition toPaCO2 andPaO2,PO2,PCO2 and blood flow in the caudate nucleus were measured continuously using chronically implanted mass spectrometer catheters and heated thermistors. Caudate nucleus blood flow increased in response to hypoxia and hypercapnia and this response was not significantly affected by section of one or both g.s.p.n., sinus or vagus nerves. With section of sinus and vagus nerves, blood flow changed passively with arterial pressure.

Muscle glycogen depletion patterns in fast twitch fibre subgroups of man during submaximal and supramaximal exercise.

Abstract: Muscle glycogen depletion in ST, FTa and FTb fibres were studied in human subjects undergoing two distinctly different modes of bicycle exercise. Two hours of submaximal exercise (60% of VO2 max) produced a 77% decline in muscle glycogen concentration accompanied by only minor elevations in muscle and blood lactate levels whereas 10 one minute supramaximal work bouts resulted in a 52% decrease in total glycogen concentration and substantially elevated muscle and blood lactate contents. Moreover the patterns of glycogen depletion in the two conditions were also distinctly different. Based on the PAS staining intensity, glycogen was depleted the most in ST fibres and least in FTb fibres, during submaximal work. During supramaximal work FTb fibres were the lightest in PAS staining, with little loss of glycogen from ST fibres. In both situations the loss of glycogen in the FTa fibres was intermediate compared to the other two fibre types. These data support a selective recruitment of muscle fibres during work of different intensities, and further, suggest a physiological basis for the subgrouping of FT fibres in man.

Effects of increasing arterial pressure on cerebral blood flow in the baboon: Influence of the sympathetic nervous system

Abstract: The influence of stimulation of the cervical sympathetic chain on the response of cerebral blood flow to hypertension induced by the intravenous infusion of angiotensin was studied in anaesthetised baboons. Cerebral blood flow was measured by the intracarotid133Xenon injection technique. Possible lesions of the blood-brain barrier were studied by injecting Evans blue towards the end of the experiment and ischaemic brain damage was assessed following perfusion fixation. In a control group of five baboons blood flow increased by 53±9% (mean ±S.E.) from the base line values in the arterial pressure range 130–159 mm Hg. In four baboons subjected to unilateral sympathetic stimulation flow increased by 16±4% in the same pressure range. In three babbons subjected to bilateral sympathetic stimulation there were not significant increases in flow until the arterial pressure had increased above 159 mm Hg. Disruption of the blood-brain barrier in the parietooccipital regions was only seen in the control animals but not in the stimulated baboons. Ischaemic brain damage was not observed with the exception of one small lesion in a single stimulated baboon. These findings provide strong support for the observations of Bill and Linder (1976) that activation of the cervical sympathetic can modify the level at which breakthrough of cerebral blood flow occurs in association with systemic hypertension.

Characteristics of Fast Excitatory Postsynaptic Current in Bullfrog Sympathetic Ganglion Cells

Abstract: The membrane current underlying the fast excitatory postsynaptic potential (EPSC) of bullfrog sympathetic ganglion cells was studied. The relationship between the EPSC amplitude and membrane potential was linear at negative levels of membrane potential, but deviated from the linearity toward a smaller amplitude at positive levels. The falling phase of EPSC almost followed a single exponential decay. The half-decay time (HDT) of EPSC's increased exponentially with an increase in the negativity of membrane potential. The rise time (RT) was also prolonged slightly with membrane hyperpolarization. Lowering of temperature decreased the EPSC amplitude, lengthened markedly the HDT and increased the slope relating the logarithm of the HDT to membrane potential. Neostigmine (1×10−5 M) prolonged both the RT and HDT. A decrease in Ca2+ concentration caused a marked reduction in the EPSC amplitude, and a slight shortening in the RT and HDT. An increase in Ca2+ concentration significantly prolonged the RT and HDT without altering the slope of the relationship between the HDT and membrane potential, while the amplitude of EPSC was increased slightly. The HDT was independent of EPSC amplitude. It is suggested that the mechanism responsible for closing the ion channels of the nicotinic receptor at the subsynaptic membrane is regulated by membrane potential. The possible mechanisms of the action of Ca2+ on the decay phase of EPSC were discussed.

Functional and metabolic features of an isolated perfused guinea pig heart performing pressure-volume work.

Abstract: Cardiac performance and some parameters of glycolytic and oxidative metabolism were analyzed in isolated perfused guinea pig hearts performing pressure-volume work. Perfusion medium was an oxygenated Krebs-Henseleit bicarbonate buffer (pH 7.4) which contained glucose and physiological concentrations of pyruvate and insulin. The pressure-flow relationship in the coronary vascular bed indicated autoregulation of coronary flow. Left ventricular function was influenced by aortic pressure (Pa) and venous filling pressure (Pv) in accordance with the Frank-Starling principle, i.e. stroke work increased as a function of Pa or Pv to a certain maximum and then decreased. Myocardial oxygen consumption (MVO2), on the other hand, was linearly correlated with Pa and Pv, respectively, over the entire pressure range. Efficiency of the left ventricle, therefore, increased to an optimum (16%) and decreased at higher pressures. Myocardial contents of glycogen, ATP and creatine phosphate were not markedly influenced by a change in Pa or Pv.l-Noradrenaline (0.08 μM, NA) stimulated stroke work and MVO2 at a all Pv tested; efficiencies reached physiologic values (21%) at high volume loads. The increased MVO2 was associated with an acceleration of pyruvate decarboxylation and lactate release up to 10- and 15-fold, respectively, at elevated but physiological NA concentrations (0.2 μM). Our results demonstrate that the isolated perfused working guinea pig heart compares favourably with the non-failing Starling heart-lung preparation and hearts in situ, as far as coronary function, left ventricular performance and oxidative metabolism are concerned.

Acetylcholine-induced potassium current fluctuations in the rabbit sino-atrial node.

Abstract: 1. Small sinoatrial-node preparations were voltage clamped by two micropipettes. Both the amplitude (mean current) and the fluctuation of acetylcholine-induced potassium current were recorded. The fluctuations were analyzed by both calculating their variance and establishing their power density spectrum. 2. It is assumed that acetylcholine receptors, when occupied, open momentarily ionic channels. Each channel is described by its conductance γ and the average open time τ. 3. The variance did not increase linearly with the mean current, but reached a saturation and even decayed with large mean currents, indicating that more than 50% of the total number of channels are open. 4. The average maximum mean current (all channels open) for a preparation approximately 300 μm ×200 μm×50 μm was 89±22 nA (n=7). 5. The average single channel conductance, calculated from the variance, was 3,71±0.48 pS (n=7). 6. The power density spectra of the fluctuations were fitted by single Lorentzian curves. The single channel conductance was thus determined to be γ= 3.79±1.25 pS and the corner frequencyfc=0.96±0.25 Hz (n=21). This corresponds to an average open time τ=166 ms. 7. TheQ10 of the average open time (determined by the corner frequency (fc) was 2.83±0.38 (n=4). 8. The density of channels was approximately 1 per 1 μm2 of cell surface or roughly 2000 channels per cell. 9. The muscarinic acetylcholine receptor of S-A node cells may thus be characterized by a relatively long open time (160 ms), a low density of channels and a small elementary conductance of about 4 pS.

Effects of halothane on caffeine-induced tension transients in functionally skinned myocardial fibers.

Abstract: The effects of halothane on caffeine-induced tension transients in functionally skinned myocardial fibers were investigated. Fiber bundles from mechanically disrupted rabbit right ventricular papillary muscles were mounted on a tension transducer. The fiber preparation was loaded with Ca2+; Ca2+ was then released by the use of caffeine (25 mM); and the area of the resulting tension transient was measured. Each preparation was sequentially transferred from control to test to control solution. The control solutions were equilibrated with 100% N2, and the test solutions with a mixture of N2 and various halothane concentrations. The preparation was exposed to halothane during the Ca2+ uptake or the release phase only, or during both Ca2+ uptake and release phases. The areas of the test tension transients were compared with those of the two control tension transients. It was found that halothane depressed the caffeine-induced tension transient either during the uptake phase or the combined-uptake-and-release phase but not during the release phase. The halothane-induced depression was dose-dependent, reversible, and comparable to the depression observed in intact isolated papillary muscles. We conclude that halothane could induce myocardial depression by inhibiting Ca2+ uptake by the sarcoplasmic reticulum.

The effect of inhibition of prostaglandin synthesis on tubuloglomerular feedback in the rat kidney.

Abstract: To further clarify the mechanism mediating the reduction of nephron filtration rate in response to an increase of loop of Henle flow rate we have studied the effect of prostaglandin inhibition on tubuloglomerular feedback in rats. Following inravenous administration of 2 or 5 mg/kg indomethacin feedback responses expressed as the percent reduction of early proximal flow rate (EPFR) during flow elevation from 0–40 nl/min decreased from control values of −54.3±4.3% (mean ± S.E.) and −39.5±3.9% to −27.9±2.8% (P<0.001) and −5.0±4.9% (P<0.001) respectively. A significant reduction in the feedback response was also seen following intravenous administration of 2 or 5 mg/kg Ro 20-5720 (−28.8±5.8% and −7.8±3.8% respectively), 10 mg/kg meclofenamate (−15±4%), and 2 mg/kg eicosa-5,8,11,14-tetraynoic acid (−16.2±4.8%). In contrast to control animals injection of 5 mg/kg indomethacin had no effect on the feedback response in rats kept on a low salt diet. After applying a single dose of 5 mg/kg indomethacin or Ro 20-5720 feedback responses were reduced to −5.4±4.3% and −3.0±4.36% in the period 0–80 min, but were normal in the period 81–160 min after injection (−36.1±2.83% and −44.3±2.82% respectively). A dose dependent inhibition of the feedback response was also noted when indomethacin was applied intraluminally with full inhibition being established at a concentration of 0.5 mM. Urinary excretion rates of PGE2 and PGF2α fell from control values of 286.1±73.7 and 143.5±25.9 pg/min to 31.2±9.9 and 23.6±9 pg/min following 2 mg/kg indomethacin and to 36.8±4.4 and 8.9±1.9 pg/min following 5 mg/kg Ro 20-5720. Reduction of PG excretion was not reversible during the time of the experiment. Our results demonstrate a consistent decrease of tubuloglomerular feedback responses during inhibition of prostaglandin biosynthesis.

Sodium reabsorption in the papillary collecting duct of rats. Effect of adrenalectomy, low Na+ diet, acetazolamide, HCO-3-free solutions and of amiloride.

Abstract: Using the shrinking droplet method and simultaneous perfusion of the peritubular capillaries the isotonic reabsorption of Ringer's solution from the papillary collecting ducts was measured. Under control conditions the volume reabsorption from the papillary collecting ducts was Jv +/- SE = 2.6 +/- 0.1 . 10(-5) cm3 . cm-2 . s-1. In rats which were on low Na+ diet, Jv increased to 127%, and in adrenalectomized animals it decreased to 34% of the control value. Three hours after a;ocatopm pf a;dpsterpme om tje adrenalectomized animals Jv was partially restored to 63% of control rats. Amiloride 10(-4) M, added to the luminal perfusate, produced a strong inhibition of Jv (to 32% of control). Acetazolamide, 10(-4) M, added to both perfusates, reduced Jv very strongly (to 40% of control), while omission of bicarbonate reduced it only to 77% of control. Acetazolamide, added to bicarbonate-free perfusates, did not result in a significant further reduction of Jv. The data indicate that the Na+ reabsorption from the papillary collecting duct is controlled by mineralocorticoids. Furthermore, they suggest the existence of two transport mechanisms in the luminal cell membrane: 1. An amiloride-sensitive entry step and 2. an entry step via a Na+-H+-countertransport mechanism, the latter being less important.

Cold-Sensitive Afferents from the Abdomen

Abstract: In cats afferent impulses from splanchnic and vagus nerve preparations were studied. In each splanchnic nerve serving the stomach or the adjacent part of the duodenum, cold-sensitive afferents could be recorded. There were also numerous mechanosensitive fibers originating from stomach, intestine, mesentery and the region of blood vessels. No thermal afferents were found in the vagus nerve. The cardiovascular and respiratory myelinated afferents were insensitive to thermal stimuli.

Independent Development of Contractile Properties and Myosin Light Chains in Embryonic Chick Fast and Slow Muscle

Abstract: 1. The contractile speeds and tetanus/twitch ratios of the slow anterior latissiumus dorsi (ALD) and fast posterior, latissimus dorsi (PLD) muscles were studied during embryonic development and correlated with the type of myosin light chains present in these muscles as studied by one and two dimensional polyacrylamide gel electrophoresis. 2. At a time when the contractions of PLD were slow, i.e. in 15 day old embryos, the myosin light chains in this muscle were of the fast type. The slow contraction of this muscle may be due to incomplete and slow activation of the contractile elements. The tetanus/twich ratio of muscles from 15 day old embryos is low and increases sharply with age. This increase could be due to the maturation of the internal membrane system, and occurs at about the same time as the increase in the speed of contraction. 3. ALD muscles contract slowly during all stages of development, although their tetanus/twitch ratio also increases with age. At 13 days they contain a mixture of fast and slow type myosin light chains and with increasing age the proportion of the slow type myosin light chains increases at the expense of the fast type. The slow time course of contraction of ALD is consistent with the presence of slow type myosin light chains. 4. The possibility that the synthesis of the slow type myosin light chains in ALD is induced by early motor activity in chick embryos is discussed.

Salivary cooling, escape reaction and heat pain in capsaicin-desensitized rats

Abstract: Salivary thermolytic mechanism (weight of salivary glands, effect of desalivation on water intake and body temperature, grooming activity) as well as escape behaviour and reaction to heat pain were studied in capsaicin-desensitized and control rats exposed to various warm ambient temperatures. Body temperature of the desensitized rats increased more than the controls at all the ambient temperatures studied (32, 34 and 36°C); however, significant differences in the mechanism of salivary cooling were obtained only at 34 and 36°C. Central impairment of saliva spreading in desensitized rats seems evident. Complete surgical desalivation did not increase hyperthermia of control and desensitized animals in warm environments. Therefore other mechanisms, primarily vasodilatatory, must also be involved in the rat's thermolytic normal response. Although desensitized rats did not show a tendency to escape from the warm environment their response to heat pain was normal. In conclusion, it is suggested that heat perception in desensitized animals is impaired; however, the existence of some capsaicin-insensitive thermolytic mechanisms (prone extension of the body) cannot be excluded.

Projection of scrotal thermal afferents to the preoptic and hypothalamic neurons in rats.

Abstract: Effects of thermal stimulation (18–41.5°C) of the scrotum were observed on neurons in the preoptic area and hypothalamus (POHY) in anesthetized rats. Changes in firing rate of POHY neurons occurred, with three exceptions, within the scrotal temperature range of 30–41°C. There was no dynamic response and little or no sign of rapid adaptation. Out of 46 warm-sensitive neurons, 34 increased and 9 decreased in firing rate with a rise in scrotal temperature. Out of 26 cold-sensitive neurons, 19 were excited and 4 were suppressed by scrotal cooling. The 3 exceptions were excited by scrotal warming above 36°C, and were also excited by cooling below 30°C. Out of 54 thermally-insensitive neurons, 16 were excited by scrotal warming, 7 by cooling and 2 by warming and cooling. The scrotal temperature change needed to produce full change in POHY neuronal activity varied from less than 1°C to 7°C, and was usually less than 4°C. Thermal stimulation of either half of the scrotum had identical influence on the same POHY neuron.