Showing papers in "Pflügers Archiv: European Journal of Physiology in 1971"

Analysis of cutaneous warm and cold fibres in primates.

Abstract: Cutaneous warm and cold receptors were examined electrophysiologically in rhesus monkeys (Macaca mulatta) by recording from single units dissected from the saphenous nerve and the superficial branch of the radial nerve. Single warm and cold fibres had spot-like receptive fields in the hairy skin which were highly specific to thermal stimuli and did not respond to mechanical deformation of the skin. One group of cutaneous warm receptors had a range of static activity between 30 and 44°C and an average static maximum of 12 imp/sec at 41°C, whereas the static maximum of the other group was at temperatures higher than 44°C. About one third of the cold fibres was myelinated, with a conduction velocity from 2.2 to 9.5 m/sec (mean 6.3 m/sec), while the remaining part was unmyelinated, having a conduction velocity of 0.3 to 1.3 m/sec (mean 0.7 m/sec). All warm fibres were non-myelinated, with a conduction velocity of 0.4 to 0.9 m/sec (mean 0.7 m/sec).

Effects of 2,3-diphosphoglycerate and other organic phosphate compounds on oxygen affinity and intracellular pH of human erythrocytes

Abstract: The effects of changes of the 2,3-DPG content and of the total concentration of organic phosphates on the oxygen affinity and the intracellular pH of human erythrocytes were studied. The oxygen affinity as characterized by the P50 (oxygen tension at 50% O2 saturation) increases from 15 to 45 mm Hg when the 2,3-DPG concentration is elevated from 0.1 to 24 μmoles/g by incubation of erythrocytes in the presence of inosine, pyruvate and phosphate. In cells containing normal concentrations of 2,3-DPG, but accumulating high amounts of other organic phosphates during incubation with inosine and phosphate, the P50 was found to rise up to 36 mm Hg. This effect as well as a considerable part of the 2,3-DPG effect on the oxygen affinity of intact erythrocytes is due to a shift of the Donnan equilibrium induced by the accumulation of non-penetrating phosphate anions and consecutive changes of the intracellular pH, which in turn alter the oxygen affinity via the Bohr effect of hemoglobin. The intracellular pH is related to the intracellular concentration of organic phosphates (extracellular pH 7.40) by the equation: $${\text{pH}}_i {\text{ }} = {\text{ 7}}.306{\text{ }} - {\text{ }}0.0083{\text{ }} \cdot {\text{ }}P_{org} {\text{ }}(\mu moles organic P/g).$$ This dependency agrees closely with the theoretical relationship between the intracellular pH and the concentration of organic phosphates calculated from the osmolarities and the net charges of non-penetrating cell constituents. After correction of the oxygen affinities to a constant intracellular pH the P50 does not further increase in cells containing 2,3-DPG concentrations above 8 μmoles/g and remains unaltered in erythrocytes accumulating other organic phosphates.

Early membrane depolarization of the fast mammalian muscle after denervation.

Abstract: The first alteration noted after denervation of the extensor digitorum longus muscles of rats was a decrease in resting membrane potential (RMP) which occurred at about 2h. The exact time course of this membrane depolarization was dependent upon the intramuscular length of the degenerating nerve stump. The decrease in RMP occurred prior to any detectable alteration in adenosine triphosphate and phosphocreatine content of the muscle. Prior to failure of spontaneous transmitter release, which occurred 10 h after denervation, some muscle fibres showed an increase in frequency of the miniature end-plate potentials (m.e.p.p.) with no alterations in amplitude and shape of the single potentials. Appearance of areas sensitive to acetylcholine (ACh) on the extra-junctional membrane occurred at 24 h after crushing the motor nerve. At 48 h after denervation a high ACh-sensitivity appeared at the muscle-tendon region, but was not detected in the majority of the muscle fibres studied midway between end-plate region and muscle-tendon area. The transverse resistance of a unit area of the muscle membrane was increased 3 days after denervation. These results provide evidence that the processes of post-denervation changes occur in the following temporal sequence: a) partial depolarization of the postsynaptic muscle membrane; b) a decrease and subsequent cessation of the spontaneous transmitter release preceded in some fibres by a transient increase in m.e.p.p. frequency; c) appearance of extrajunctional ACh sensitivity; d) increase in the transverse resistance of a unit area of the muscle membrane. It is suggested that the motor nerve releases more than one neurotrophic substance.

Control by Insulin of Sodium Potassium and Water Excretion by the Isolated Dog Kidney

Abstract: Insulin has been shown to decrease sodium, potassium and water excretion by direct action on the kidney. Reduction of sodium excretion is due to enhanced tubular reabsorption as a probable consequence of stimulated active sodium transport. The renal effect of insulin is demonstrated with plasma hormone concentration observable in pathophysiological conditions; it offers therefore a possible explanation for some clinical findings such as the changes in sodium, potassium and water excretion occurring in man after fasting and subsequent glucose feeding.

Modulation of sensory transmission in cat lemniscal system during voluntary movement.

Abstract: Adult cats were trained to lift their forepaw, depress a lever and then replace their paw on the ground. The potential recorded in the medial lemniscus to stimulation of the superficial radial nerve in the forelimb involved in the movement is depressed both prior to and during displacement of the limb. These changes did not result from movement of the stimulating electrode. The timing of the suppression in lemniscal transmission suggests a central origin of this effect.

Slow inward current and action potential in cardiac Purkinje fibres

Abstract: The slow inward current in short Purkinje fibres was studied in voltage clamp experiments. The results were as follows: 1. The slow inward current displayed as inward tail current on repolarization can be inactivated by conditioning depolarization. Thereby the outward current during the depolarization step was slightly increased. This result indicates that in the net outward current flowing during depolarization slow inward current and dynamic outward current overlap. 2. Mn++ ions caused shortening of the action potential and blocked the slow inward current elicited either by depolarization or repolarization (inward tail current). Thereby the dynamic outward current was often increased (see 1.). An effect of Mn++ ions (7–10 mM) on the outward currents (dynamic and steady-state current) was not observed. 3. The inward tail currents on repolarization were reduced by about one half when the extracellular sodium was replaced by cholinchloride. The residual inward tail current was further reduced on lowering the extracellular calcium concentration and it was increased on increasing the calcium concentration in the bathing solution. In Tyrode's solution (150 mM Na) lowering the calcium concentration strongly reduced the tail current, presumably by reducing the contribution of calcium ions to the tail current and/or by a rise in intracellular sodium, resulting in a decrease of the contribution of the sodium ions to the tail current. The effects of several combinations of reduction in both sodium and calcium ions on the tail current were not additive: the effect of sodium reduction was smaller at lower than at normal extracellular calcium concentrations. 4. The instantaneous conductance of the slow inward current was found constant at potentials negative to −25 mV but could not be determined positive to −25 mV because of large overlapping outward current. 5. The current voltage relation of the slow inward current was estimated. The current seems to be maximum between −20 mV and zero mV. 6. The inactivation of the slow inward current was slower at low and faster at high negative membrane potentials. 7. On clamping the potential during the action potential a rising outward current flowed which was not seen in presence of Mn++ ions indicating that this rising outward current is in fact due to decline of the slow inward current.

On the mechanisms of the hypoxia-induced increase of 2,3-diphosphoglycerate in erythrocytes. Studies on rat erythrocytes in vivo and on human erythrocytes in vitro.

Abstract: Hypoxia induces in rats a rather rapid increase of the concentration of 2,3-DPG in red blood cells. This increase is reversed when the animals are returned to normal conditions. Pigeons do not respond to hypoxia with an increase of inositol hexaphosphate concentration in their erythrocytes. In rats exposed for 24 h to gas mixtures containing low oxygen and in addition 5% CO2 the hypoxia induced rise of 2,3-DPG concentration is abolished. The hemoglobin concentration in whole blood is negatively correlated to red cell 2,3-DPG levels in normal as well as in anemic or polycythemic rats. The rate of 2,3-DPG decomposition in human erythrocytes incubated without glucose is the same in the presence and in the absence of oxygen. The incorporation of32P into 2,3-DPG proceeds faster in deoxygenated than in oxygenated human red blood cells and exceeds considerably the concomitant acceleration of the glycolytic flux rate. These findings indicate that the rate of 2,3-DPG synthesis becomes enhanced in deoxygenated cells. This is mainly due to an elevation of the intracellular pH; the relief of product inhibition of DPG mutase brought about by a greater binding of 2,3-DPG to deoxyhemoglobin seems to be of minor importance. The regulation of 2,3-DPG concentration by the intraerythrocytic pH as well as by the oxygenation state of hemoglobin and the significance of these regulatory mechanisms in inducing and limiting the changes of red cell 2,3-DPG during hypoxia and anemia are discussed.

Feedback interaction of mechanical and electrical events in the isolated mammalian ventricular myocardium (cat papillary muscle)

Abstract: Measurements of transmembrane potentials were performed under different contractile conditions on isolated cat papillary muscles. It was found that the duration of the action potential (within limits of about 20%) depends on the mode of contraction. Isotonic shortening tends to prolong, isometric tension development tends to shorten the duration of the action potential. As a result of the action potential alterations negative or positive inotropic mechanical transients are observed during 5–10 subsequent beats. The decrease in action potential duration is roughly proportional to the force development, and the increase of action potential duration is related to the shortening velocity. By applying a controlled stretch the shortening velocity of the contractile element (V CE ) was reduced below its value during purely isometric conditions. A further decrease of the action potential duration was observed. IncreasingV CE by release experiments increased the action potential duration beyond that observed under lightly loaded isotonic contractions. A quick release taking place after repolarization is complete produces a new distinct wave of depolarization (10–15 mV) which can sometimes initiate a new action potential. The quick release experiments fascilitated the estimation of the time delay of the feedback interaction which is less than 10 msecs. The possibility that passive geometrical changes of the plasma membrane is a causitive factor of the described phenomenon was experimentally excluded. Alternative explanations are discussed. It seems likely that a controlling parameter of this excitation contraction feedback system is contained in the force velocity relation of the contractile element influencing the internal Ca++-transients by its mode of contraction.

The localization of the Na + -K + -ATPase in the cells of rat kidney cortex. A study on isolated plasma membranes.

Abstract: Plasma membrane fractions of rat kidney cortex were subdivided by centrifugation on a continuous and a discontinuous sucrose gradient and by carrier free continuous electrophoresis. In the different fractions the activity of alkaline phosphatase and aminopeptidase, enzymes which are present in the brushborder membrane, as well as Mg++-ATPase, Na+−K+-ATPase, 5′-nucleotidase, acid phosphatase and glucose-6-phosphatase were determined. The distribution of alkaline phosphatase, aminopeptidase and 5′-nucleotidase is identical, indicating the localization of these enzymes in the brushborder membrane. Na+−K+-ATPase does not show an identical distribution with any of the enzymes studied. Using carrier free continuous electrophoresis fractions can be obtained which are enriched in alkaline phosphatase by a factor of 15 when compared to the cortex homogenate, whereas the specific activity of Na+−K+-ATPase is reduced to one third of the starting material. On the other hand fractions can be isolated in which the specific activity of Na+−K+-ATPase is 16 times higher than in the homogenate. No enrichment of alkaline phosphatase occurs in these fractions. It is therefore concluded that the Na+−K+-ATPase is not present in the brushborder membrane nor in the lysosomes or endoplasmatic reticulum. The most probable localization of the Na+−K+-ATPase are the basal infoldings of the plasma membranes of the cells.

The role of bicarbonate and other buffers on isotonic fluid absorption in the proximal convolution of the rat kidney

Abstract: The fluid reabsorption from the proximal convolution of the rat kidney was measured with the Gertz shrinking droplet technique Simultaneously, the peritubular capillaries were perfused with artificial solutions In some experimental series, fluid from the shrinking droplet was withdrawn and analysed for Cl−, Na+, and osmolality so that the transtubular transport of Na+, Cl−, and HCO 3 − could be calculated Capillary perfusate in some experiments was also withdrawn and its pH was measured The following results were obtained: 1 With increasing concentration of HCO 3 − in the capillary perfusate, the transtubular water, sodium, chloride, and bicarbonate reabsorption increased 2 The sulfonamide buffers sulfamerazine and glycodiazine (Redul®), which easily penetrate the tubular wall, could, in equimolar concentrations, substitute totally for the bicarbonate buffer in promoting isotonic fluid absorption 3 Butyrate, propionate, and acetate were also effective; pyruvate, lactate, and paraaminohippurate, however, were not 4 The effect of HCO 3 − and glycodiazine on isotonic absorption was shown to depend exclusively on the concentration of the buffer anion and not on the concentration of undissociated acid or pH From these data it is suggested that for proximal isotonic absorption of water, sodium, and chloride, the reabsorption of buffer anions via H+ secretion and nonionic diffusion may be essential The H+ secretion or the buffer anion absorption across the luminal cell wall may secondarily influence the active Na+ transporting mechanism located at the basal cell site either by a luminal H+−Na+ exchange mechanism or by a lyotropic effect which would increase the Na+ permeability of the luminal cell site Thereby more Na+ would be delivered to the Na+ pumping site and the rate of Na+ pumping would be augmented

Activation of vascular smooth muscle of rat aorta by noradrenaline and depolarization: Two different mechanisms

Abstract: 1. Contraction of helical strips of the rat aorta was induced by 3 μg/ml of noradrenaline or by potassium-rich solution (80–120 mM K). The resulting amplitudes of contraction were maximal for these respective ways of activation and showed almost the same value in this preparation. 2. The noradrenaline-induced tension, but not the contraction induced by depolarization, decreased, when the hydrogen ion concentration of the bath solution was increased. Furthermore, the response to noradrenaline was more sensitive to a blockade of the adrenergic alpha-receptors or a variation of the bath temperature. 3. Since, after the application of papaverine, the amplitudes of contraction produced by noradrenaline or depolarization were diminished to the same degree, papaverine probably acts on the later steps of the activation-contraction mechanism. 4. When verapamil (iproveratril) was applied in order to inhibit excitationcontraction coupling, tension development after depolarization was influenced to a higher degree than noradrenaline-induced contraction. 5. The fact that it is possible to inhibit the response to depolarization without substantial influence on the response to noradrenaline andvice versa led to the conclusion that in the rat aorta depolarization on the one hand and noradrenaline on the other hand act via different mechanisms of activation.

Evidence of a paracellular pathway for ion flow in the kidney proximal tubule: Electromicroscopic demonstration of lanthanum precipitate in the tight junction

Abstract: In the doubly perfused toad kidney, lanthanum ions were included in the perfusion fluid in a soluble form and were subsequently precipitated as anthanum sulfate. The precipitate was localized by electronmicroscopy. Precipitate was mainly observed at the tight junctions and in the intercellular spaces. Practically no lanthanum was observed within the cells. This work locates the paracellular pathway for ion flow proposed from electrophysiological studies (refs. [1–3, 16]) at the level of the tight junctions and of the intercellular spaces.

Regional differentiation of sympathetic activity during hypothalamic heating and cooling in anesthetized rabbits.

Abstract: In anesthetized rabbits immobilized with succinyl choline, the discharges of sympathetic efferents supplying cutaneous and visceral regions were simultaneously recorded. The effects of thermal stimulation of the hypothalamic region were tested on the basis of the integrated discharges. During hypothalamic heating cutaneous sympathetic activity decreased, corresponding to increased ear blood flow, while visceral sympathetic activity increased. During hypothalamic cooling there was, on the average, no significant change of regional sympathetic activity. However, in single experimental periods an increase of cutaneous and a decrease of visceral sympathetic activity was found.

Spinal cord and hypothalamus as core sensors of temperature in the conscious dog. I. Equivalence of responses.

Abstract: In two conscious dogs in standardized environments, the temperatures of spinal cord or hypothalamus were altered independently of each other and the resulting changes in heat production (shivering) and in respiratory evaporative heat loss (panting) were measured and correlated with these changes in temperatures. Spinal cord cooling at 18 and 24°C air temperature increased heat production by about −0.7 Kcal/(kg·h·°C). The mean spinal cord temperature at which this occurred was between 37.30 and 37.80°C. Under the same conditions hypothalamic cooling increased heat production by about −0.7 Kcal/(kg·h·°C). The temperature at which this occurred was between 38.40 and 38.75°C. Spinal cord heating at 18, 24, and 30°C air temperature increased the respiratory evaporative heat loss by +0.9 to 1.2 Kcal/(kg·h·°C) above a mean spinal cord temperature between 40.00 and 41.50°C. Hypothalamic heating at 30°C air temperature increased the respiratory evaporative heat loss by +0.9 Kcal/(kg·h·°C). For all environments the hypothalamic threshold temperature lay between 38.75 and 42.40°C. The results suggest that in the dog, spinal cord and hypothalamus represent basically equivalent core sensors of temperature.

Stretch activation and myogenic oscillation of isolated contractile structures of heart muscle.

Abstract: Glycerinated or freeze-dryed fibre bundles of heart muscles (papillary and trabecular muscles of rabbit or guinea pig) show in ATP-salt solution with about 10−6M Ca2+ an active, delayed tension increment after quick or sinusoidal stretching The active tension increase is completely different from the passive tension increment caused by stretching of the elastic structures of the muscle; this well known length dependence of tension is also in phase with the length changes (or the tension-phase preceeds the length-phase in visco-elastic bodies) On the other hand, the active tension increase is delayed with respect to the length change; this can be observed very well after rectangular changes in length The delayed activation of the contractile bonds at stretch and the delayed deactivation at shortening induce the muscle-during sinusoidal length changes in a characteristic frequency range-to produce power output The frequency range corresponds to the heart beat frequency of the living muscle Temperature rise and inorganic phosphate accelerate, Mg-ions and ADP retard the contraction speed Ca-ions influence only the amount of the isometric tension, but not the contractile velocity

Kinetics of Na inactivation in frog atria.

Abstract: 1. In frog atria, time and voltage dependence of inactivation and reactivation of fast transient Na current were studied using the sucrose-gap voltage clamp technique. Experiments were done at 4–7° C. 2. Fast inward current inactivated by conditioning depolarizing clamps. The relation between steady-state inactivation and membrane potential is represented by an S-shaped curve similar to that observed in squid axon. At the resting level the availability of the Na-carrying system is about 60–70%. 3. During depolarizing clamps inactivation of Na current follows an approximately exponential time course with time constants between 1.5 and 8 msec. 4. Recovery from inactivation (reactivation) is much slower than development of inactivation. Time constants between 100 and 600 msec were observed during the recovery process following a repolarization or a hyperpolarization. 5. A ratio between the time constants of inactivation and reactivation in the order of 1∶50 was found when the two processes were studied at the same potential level. 6. In the frog atrial action potential the slow reactivation of the Na system is reflected by a relative refractory period reaching far beyond full repolarization. 7. Assuming that the slow course of Na reactivation is an inherent feature of Na kinetics, the inactivation variable (h) of the Hodgkin-Huxley theory (1952d) seems inadequate to describe the inactivation-reactivation process in frog atria. Formally fast inactivation and slow reactivation could be accounted for by replacing the variableh with two variables which both decrease on depolarization but largely differ in the rate constants.

The dependence of cardiac contraction on depolarization and slow inward current.

Abstract: The membrane potential of the guinea-pig's papillary muscle was controlled by a voltage clamp technique which employs one sucrose gap and one intracellular microelectrode. Both the membrane potential and the membrane current were recorded together with the contraction. The steady-state contractions were obtained after 6–8 contractions. The difference between the steady-state contractions and the succeeding test contractions was considered to be due to the difference in the trigger action between the conditioning and the test pulses. The following results were obtained: 1. when the test pulses were appropriately shortened so that a large tail of inward current flowed after the repolarization step, the contraction was augmented. This paradoxical increase of the contraction can be explained by assuming a direct action of the slow inward current on contraction. 2. The peak amplitude of the contraction increased with the size of the depolarizing step in the range of the membrane potential at which the calcium current should be small or zero. This suggests that in addition to the calcium current another effect of depolarization controls the contraction. 3. The rate of rise of contraction seemed to be determined by the calcium current which was maximum at a depolarization to +10 mV. At this level the slow inward current also reached the maximum. With further increase of the depolarization the rise of the contraction and the slow inward current were decreased. 4. During a series of the pulses the positive inotropic effect (staircase) was the more pronounced the larger the depolarization. This holds true for depolarization up to +70 mV. The potentiation occurred in spite of decrease of the slow inward current. It seems necessary to postulate a potentiating process which is dependent on the amplitude of the depolarization.

Potassium inactivation in single myelinated nerve fibres of Xenopus laevis

Abstract: 1. Voltage clamp measurements were performed on single myelinated nerve fibres of the frog Xenopus laevis. 2. During long-lasting depolarizations the potassium current decayed in a fast phase with a time constant of about 0.6 sec and a following slow phase with a time constant between 3.6 (V=0) and 20 sec (V=100 mV). 3. The decay of the potassium current was the result of an inactivation of the potassium permeability and not of a shift of the potassium equilibrium potential as shown by experiments in isotonic KCl solution. 4. At a hyperpolarization of −20 mV the potassium inactivation was fully removed. It remained incomplete even at large depolarizations. The steady-state inactivation curve was S-shaped but not symmetrical. 5. The experimental results could be described by extending the Hodgkin-Huxley equations introducing two terms of potassium inactivation.

The effect of a sympatho- and a parasympathomimetic drug on the electrolyte concentrations of primary and final saliva of the rat submaxillary gland.

Abstract: Salivary glands are generally supposed to produce their secretions in 2 stages: 1. A plasma-like secretion is formed in the acinar-intercalated duct region of the gland, the rate of production but not the electrolyte composition of this fluid being increased by gland stimulation. 2. This primary saliva is then modified during its passage along the gland duct system by processes of Na reabsorption and K and HCO3 secretion.

Changes in the interstitial pH of dog myocardium in response to local ischemia, hypoxia, hyper- and hypocapnia, measured continuously by means of glass microelectrodes

Abstract: In open-chest dogs the pH changes of the myocardial interstitium were measured during local ischemia, hypoxia, hyper- and hypocapnia. Microglasselectrodes (Corning 0150) were inserted into the wall of the left ventricle. Simultaneously we recorded the local myocardial blood flow, the arterial blood pressure, the heart rate and the expiratory CO2 concentration. Local ischemia was produced by transient occlusion of the left descending coronary artery. In the ischemic region a decrease in pH occurred after 15–30 sec, the magnitude of which depended on the occlusion time, and on the extent of the ischemic region. When the occlusion time was short, the maximum decrease in pH was found after the release of blood flow. Mean values varied from about 0.1 pH (1 min occlusion) to 0.65 pH (30 min occlusion). After fibrillation the pH fell by 1.2 units (mean value) below the initial level. Hypoxia (10% for 5–13 min) was accompanied by an increase in pH by 0.05–0.1 units. After 2–3 min the pH reached a steady state or decreased again. After ventilation with sufficient O2 concentration an acidotic overshoot occurred (0.03-0.1 pH). When shifts in the interstitial pH similar to those during ischemia and hypoxia were produced by varying the arterialpCO2, no comparable changes in local blood flow and in the other parameters could be observed.

Maximal elevation of 2,3-diphosphoglycerate concentrations in human erythrocytes: influence on glycolytic metabolism and intracellular pH.

Abstract: The 2,3-DPG content of human red blood cells can be elevated in vitro to a maximum of 24 μMoles/g by incubating the cells in media containing inosine, pyruvate and inorganic phosphate (=IPP media). The rate of accumulation depends on the extracellular phosphate level. The concentrations of organic phosphate fractions other than 2,3-DPG also increase during the initial phase of incubation in IPP media, but rediminish thereafter. As a consequence of these changes, the total concentration of acid-soluble organic phosphates in the red cells rises from 14 to 55 μMoles P/g red cells. This increase of non-penetrating anions produces a shifting of the Donnan ratio H e +/H i + to lower values and thereby diminishes progressively the intracellular pH of the red cells during incubation in IPP media. The extent of these changes can be calculated on the basis of equations derived by van Slyke. The Donnan induced intracellular acidification causes a gradual impairment of red cell metabolism as the 2,3-DPG concentration increases, thus imposing a selflimitation to the accumulation of 2,3-DPG in the presence of IPP and leading to an inhibition of glucose consumption in IPP-pretreated cells. The findings are discussed with respect to their metabolic and biophysical basis and in view of possible implications for the regulation of red cell metabolism and function.

Norepinephrine and potassium fluxes in cardiac Purkinje fibers.

Abstract: Dog ventricular Purkinje fibers, loaded with42K, were mounted in a tissue bath located over a beta-detector and washed in Tyrode solution. Tissue radioactivity was measured at intervals and transmembrane potential recorded by means of microelectrodes. Relative potassium influx was estimated by re-exposing the fiber to radioactive solution for fixed periods and measuring the tissue radio-activity increase at the end of the uptake period. Potassium efflux was estimated by measuring tissue and effluent radioactivities. After control recordings, administration of norepinephrine caused the following changes during the period it was applied: 1. increase in potassium influx; 2. increase in potassium efflux in nonstimulated fibers; 3. a smaller increase in potassium efflux in fibers stimulated electrically at a constant rate; 4. increase in potassium content in fibers loaded to equilibrium with42K; 5. a smaller increase in K uptake in fibers driven at a high rate; and 6. enhancement of potassium uptake even in the presence of high [K]0. It is concluded that norepinephrine increases both influx and efflux in Purkinje fibers. The larger enhancement of the influx with respect to the efflux and the increase in potassium content suggests that norepinephrine stimulates active transport of potassium. This stimulatory action can be dissociated from the stimulation of automaticity.

Anoxia-recovery cycle in ventricular muscle: action potential duration, contractility and ATP content.

Abstract: The action potential duration, tension, time to peak tension, mean rate of tension development, and ATP content of guinea pig ventricular muscle declined during 60 min of anoxic incubation. The decline in tension was closecorrelated with the decline in mean rate of tension development, whereas time to peak tension decreased in an S-shaped relationship with action potential duration decrease. When muscles were incubated under anoxic conditions for 5, 30, or 60 min then under control conditions for 30 min, the action potential duration and time to peak tension returned to control level; tension, mean rate of development, and ATP content did not recover to control level when the period of anoxia exceeded 5 min. During the first 10 min of re-oxygenation a transient overshoot of control value was noted in action potential duration and time to peak tension. The transient increase in time to peak tension was accompanied by a transient increase in tension. It was not dependent on the occurrence, or degree, of overshoot in action potential duration. Transient changes did not occur in mean rate of tension development. It has been concluded that the anoxia-induced decrease in tension is due to a decrease in the rate of tension development as a result of a decreased ATP suppl. Time to peak tension seems related to action potential duration and both are independent oftotal muscle ATP content.

Sensory transmission of spinal heat and cold sensitivity in ascending spinal neurons.

Abstract: In anesthetized cats, mostly spinalized at C1/C2, the thoracic and lumbar sections of the vertebral canal were selectively heated or cooled. Single unit activity was recorded with steel microelectrodes from the spinal cord at the level of C2 to C4. The positions of the electrode tips were determined by micromarking. The existence of two groups of temperature dependent ascending spinal units was confirmed. One group of units was activated by spinal cord cooling below normal body temperature. The other group was activated by spinal cord heating. No temperature dependent neurons were found, so far, exhibiting maximum discharge rates at normal body temperature. A roughly proportional relation between discharge rate and vertebral canal temperature seemed to exist in both heat sensitive and cold sensitive units within a limited range of spinal hyperthermia or hypothermia respectively. Part of the units exhibited dynamic responses to changes of vertebral canal temperature in addition to their static responses. As determined by micromarking, heat sensitive and cold sensitive ascending spinal units were conducted in the anterolateral tracts. Both types of units were observed also under neuromuscular blockage. It is concluded that the temperature dependent ascending spinal neurons are transmitting signals from basically afferent spinal thermosensitive structures existing as two functionally different sets, one heat sensitive and one cold sensitive.

Effect of iontophoretically applied biogenic amines and of cholinomimetic substances upon the activity of neurons in the superior colliculus and mesencephalic reticular formation of the cat

Abstract: 1. The effects of iontophoretically applied cholinomimetic substances and of biogenic amines were tested in movement sensitive neurons of the colliculus superior and in neurons of the subtectal mesencephalic reticular formation. 2. Most collicular neurons were strongly excited by Glutamate which prevented neuronal adaptation and restored excitability in totally habituated neurons. GABA proved to be a strong depressant of collicular neurons. 3. Serotonine, Noradrenaline and Dopamine effectively depressed spontaneous, Gl-induced and stimulus driven activity of collicular units. Some units were selectively responsive to Serotonine, or to Catecholamines; others responded equally well to either group of substances. This suggests the existence of separate Serotonine respectively Catecholamine receptors. 4. Only a small proportion of collicular units (7%) was excited or depressed by cholinomimetic substrances. 5. The pharmacological properties of reticular units corresponded essentially to those of collicular neurons: GABA, Serotonine, Noradrenaline and Dopamine proved to be strong depressants of spontaneous, Gl-induced and stimulus driven activity. Selective responsiveness to Serotonine or to Catecholamines was found in some neurons. Cholinomimetic substances failed to influence a significant proportion of reticular units. Glutamate application produced strong excitation and led to an increase of somato-sensory receptive fields.

Na K stimulated adenosinetriphosphatase: intracellular localisation within the proximal tubule of the rat nephron.

Abstract: With refinements of quantitative histochemistry, i.e. oilwell technique, enzymaticP ianalysis and NADP/NADPH cycling an enzymatic polarization of the tubular epithelial cell from the rat nephron to NaKATPase can be established. NaKATPase activity is limited to the basal area of the epithelial cell. Brush border fragments lack NaKATPase activity.

Adenosinetriphosphate partition in cardiac muscle with respect to transmembrane electrical activity.

Abstract: The sensitivity of guinea-pig papillary muscle transmembrane electrical activity to alterations in medium glucose concentration increased with time of incubation under anoxic conditions. DNP at a concentration of 10−4 M produced a decrease in fresh papillary muscle action potential duration comparable to that produced by low medium glucose in muscle after prolonged anoxic incubation. 10−6 M DNP did not increase the decline in action potential duration of fresh papillary muscle caused by anoxic incubation in medium containing 5 mM glucose. The ATP content of ventricular strips fell to about 30% control during 60 min of anoxia but was maintained at a significantly higher level when the medium contained 50 mM rather than 5 mM glucose. In the presence of 10−4 M DNP the ATP content of strips fell to 25% control in 10 min and the increased loss was maintained throughout 60 min. During 120 min incubation in medium containing 5 mM glucose and oxygen, the ATP of strips was maintained but the action potential duration declined to 50% control. The results support the proposal that a close association exists between glycolytically produced ATP and transmembrane electrical activity. The effects of DNP on transmembrane electrical activity may be explained by an active depletion of ATP in addition to its uncoupling activity.

The diffusion of carbon dioxide in erythrocytes and hemoglobin solutions.

Abstract: The CO2 diffusion constant (Krogh's diffusion constant) has been estimated from the CO2 flux across layers with defined thickness under steady state conditions. At 22°C and in hemoglobin solutions with a concentration of 33 g% the diffusion constant for CO2 was found to be 3.3×10−4 cm2 min−1 atm−1. This value is about 40% of the diffusion constant for CO2 in water. The relationship between the diffusion constant and the hemoglobin concentration was approximately linear in a concentration range of 10–40 g%. The temperature coefficient of the diffusion constant was −0.5%/°C both in water and hemoglobin solutions. At 38°C and in a hemoglobin solution with a concentration of 33 g%, the diffusion constant for CO2 was therefore 3.0×10−4 cm2 min−1 atm−1, the diffusion coefficient 11×10−6 cm2 s−1. A general theory for the diffusion of CO2 in hemoglobin solutions has been derived. According to this theory the diminution of the CO2 diffusion in hemoglobin solutions in comparison to water can be explained quantitatively by a reduction of the water space by the hemoglobin molecules. The diffusion constant for CO2 in layers of erythrocytes was insignificantly (0–3%) smaller than in hemoglobin solutions with the same hemoglobin concentration. It is concluded that the erythrocyte membrane does not offer a considerable resistance for the CO2 diffusion.

Foveal perceptive fields in the human visual system measured with simultaneous contrast in grids and bars

Abstract: Foveal perceptive fields (center plus surround) for human vision were investigated by means of contrast illusions in grids and bars. The task consisted of determining the size of the retinal area within which photic stimulation of the periphery induces apparent brightness changes of the central portions. The mean of the individual thresholds obtained in four experiments suggests a total field diameter of 17.8 min of arc (with an estimated 4.0′ corresponding to the center) for on-and off-center fields. It is assumed that this average value refers to perceptive fields of retinal ganglion cells. The significance of eye movements and afterimages in contrast vision and their possible influence on these measurements is discussed.

Reexamination of the split oil droplet method as applied to kidney tubules.

Abstract: The technique and evaluation of the split oil drop method of Gertz was reexamined in rats with a view to defining the correct dimension in which the results should be expressed so that the point of reference for reabsorptive capacity thus obtained be uninfluenced by the geometry of the tubule.