This review examines the properties and roles of the four types of K+ channels that have been identified in the cell membrane of arterial smooth muscle cells. 1) Voltage-dependent K+ (KV) channels increase their activity with membrane depolarization and are important regulators of smooth muscle membrane potential in response to depolarizing stimuli. 2) Ca(2+)-activated K+ (KCa) channels respond to changes in intracellular Ca2+ to regulate membrane potential and play an important role in the control of myogenic tone in small arteries. 3) Inward rectifier K+ (KIR) channels regulate membrane potential in smooth muscle cells from several types of resistance arteries and may be responsible for external K(+)-induced dilations. 4) ATP-sensitive K+ (KATP) channels respond to changes in cellular metabolism and are targets of a variety of vasodilating stimuli. The main conclusions of this review are: 1) regulation of arterial smooth muscle membrane potential through activation or inhibition of K+ channel activity provides an important mechanism to dilate or constrict arteries; 2) KV, KCa, KIR, and KATP channels serve unique functions in the regulation of arterial smooth muscle membrane potential; and 3) K+ channels integrate a variety of vasoactive signals to dilate or constrict arteries through regulation of the membrane potential in arterial smooth muscle.

https://www.physiology.org/doi/pdf/10.1152/ajpcell.1995.268.4.C799

Physiological roles and properties of potassium channels in arterial smooth muscle

Lang, Florian, Gillian L. Busch, Markus Ritter, Harald Volkl, Siegfried Waldegger, Erich Gulbins, and Dieter Haussinger. Functional Significance of Cell Volume Regulatory Mechanisms. Physiol. Rev. ...

Functional Significance of Cell Volume Regulatory Mechanisms

Renin-angiotensin system: biochemistry and mechanisms of action.

The brain is critically dependent on a continuous supply of blood to function. Therefore, the cerebral vasculature is endowed with neurovascular control mechanisms that assure that the blood supply of the brain is commensurate to the energy needs of its cellular constituents. The regulation of cerebral blood flow (CBF) during brain activity involves the coordinated interaction of neurons, glia, and vascular cells. Thus, whereas neurons and glia generate the signals initiating the vasodilation, endothelial cells, pericytes, and smooth muscle cells act in concert to transduce these signals into carefully orchestrated vascular changes that lead to CBF increases focused to the activated area and temporally linked to the period of activation. Neurovascular coupling is disrupted in pathological conditions, such as hypertension, Alzheimer disease, and ischemic stroke. Consequently, CBF is no longer matched to the metabolic requirements of the tissue. This cerebrovascular dysregulation is mediated in large part by the deleterious action of reactive oxygen species on cerebral blood vessels. A major source of cerebral vascular radicals in models of hypertension and Alzheimer disease is the enzyme NADPH oxidase. These findings, collectively, highlight the importance of neurovascular coupling to the health of the normal brain and suggest a therapeutic target for improving brain function in pathologies associated with cerebrovascular dysfunction.

Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease

The discovery of aquaporin-1 (AQP1) answered the long-standing biophysical question of how water specifically crosses biological membranes. In the kidney, at least seven aquaporins are expressed at distinct sites. AQP1 is extremely abundant in the proximal tubule and descending thin limb and is essential for urinary concentration. AQP2 is exclusively expressed in the principal cells of the connecting tubule and collecting duct and is the predominant vasopressin-regulated water channel. AQP3 and AQP4 are both present in the basolateral plasma membrane of collecting duct principal cells and represent exit pathways for water reabsorbed apically via AQP2. Studies in patients and transgenic mice have demonstrated that both AQP2 and AQP3 are essential for urinary concentration. Three additional aquaporins are present in the kidney. AQP6 is present in intracellular vesicles in collecting duct intercalated cells, and AQP8 is present intracellularly at low abundance in proximal tubules and collecting duct principal cells, but the physiological function of these two channels remains undefined. AQP7 is abundant in the brush border of proximal tubule cells and is likely to be involved in proximal tubule water reabsorption. Body water balance is tightly regulated by vasopressin, and multiple studies now have underscored the essential roles of AQP2 in this. Vasopressin regulates acutely the water permeability of the kidney collecting duct by trafficking of AQP2 from intracellular vesicles to the apical plasma membrane. The long-term adaptational changes in body water balance are controlled in part by regulated changes in AQP2 and AQP3 expression levels. Lack of functional AQP2 is seen in primary forms of diabetes insipidus, and reduced expression and targeting are seen in several diseases associated with urinary concentrating defects such as acquired nephrogenic diabetes insipidus, postobstructive polyuria, as well as acute and chronic renal failure. In contrast, in conditions with water retention such as severe congestive heart failure, pregnancy, and syndrome of inappropriate antidiuretic hormone secretion, both AQP2 expression levels and apical plasma membrane targetting are increased, suggesting a role for AQP2 in the development of water retention. Continued analysis of the aquaporins is providing detailed molecular insight into the fundamental physiology and pathophysiology of water balance and water balance disorders.

Aquaporins in the Kidney: From Molecules to Medicine

The effects of and the interaction between local perivascular variation in potassium and bicarbonate concentration on the diameter of pial arteries were studied in cats by the microapplication technique. At 11 mEq/liter of bicarbonate, a direct correlation existed between vascular diameter and K+ concentrations between 0 and 10 mEq/liter. At K+ concentrations between 10 and 20 mEq/liter, no further increase in vascular diameter was observed. At a K+ concentration of 5 mEq/liter, an inverse relationship existed between pial arterial diameter and perivascular bicarbonate concentrations between 0 and 22 mEq/liter. At K+ concentrations of 0 and 10 mEq/liter, the pial arterial diameter was determined strongly by the K+ concentration and was only slightly, if at all, influenced by bicarbonate concentrations between 5 and 22 mEq/liter. At lower bicarbonate concentrations the local acidity induced a marked vasodilation. The results indicate that the diameter of pial arterioles in cats is affected by periarteriola...

Perivascular Potassium and pH as Determinants of Local Pial Arterial Diameter in Cats A MICROAPPLICATION STUDY

Single nephron filtration rates of superficial and juxtamedullary nephrons were determined in high and low sodium rats. Single nephron GFR was calculated from TF/P inulin and tubular flow rate in superficial nephrons and single juxtamedullary GFR from corresponding data in long loops of Henle. In low sodium rats superficial nephron GFR was 23.5±6.4 (SD)×10−6 ml/min×g KW, juxtamedullary nephron GFR was 58.2±13.6 and total kidney GFR (C
In) was 0.94±0.16 ml/min×g KW. Using these single nephron values, total kidney GFR and a total number of 30,000 glomeruli per kidney, the number of superficial and juxtamedullary glomeruli was calculated to be 23,267 and 6,733, respectively. During high sodium diet superficial nephron GFR increased to 38.1±11.3 and single juxtamedullary GFR decreased to 16.5±6.6, total kidney GFR increasing to 1.01±0.24. Calculation again revealed the same distribution of the two nephron types. End-proximal TF/P inulin in superficial nephrons was 2.36±0.36 in low sodium and 2.31±0.28 in high sodium rats. Loops of Henle TF/P inulin and intratubular flow rate were inversely related: the highest TF/P inulin values and lowest intratubular flow rates were found in the descending limb. These data quantify the distribution of superficial and juxtamedullary nephrons on a functional basis and suggest a mechanism by which the kidney adjusts sodium excretion by altering the contribution of each nephron type to total kidney GFR.

Micropuncture studies on the filtration rate of single superficial and juxtamedullary glomeruli in the rat kidney.

For elucidation of the functional organization of frog skin epithelium with regard to transepithelial Na transport, electrolyte concentrations in individual epithelial cells were determined by electron microprobe analysis. The measurements were performed on 1-μm thick freeze-dried cryosections by an energy-dispersive X-ray detecting system. Quantification of the electrolyte concentrations was achieved by comparing the X-ray intensities obtained in the cells with those of an internal albumin standard. The granular, spiny, and germinal cells, which constitute the various layers of the epithelium, showed an identical behavior of their Na and K concentrations under all experimental conditions. In the control, both sides of the skin bathed in frog Ringer's solution, the mean cellular concentrations (in mmole/kg wet wt) were 9 for Na and 118 for K. Almost no change in the cellular Na occurred when the inside bathing solution was replaced by a Na-free isotonic Ringer's solution, whereas replacing the outside solution by distilled water resulted in a decrease of Na to almost zero in all layers. Inhibition of the transepithelial Na transport by ouabain (10−4
m) produced an increase in Na to 109 and a decrease in K to 16. The effect of ouabain on the cellular Na and K concentrations was completely cancelled when the Na influx from the outside was prevented, either by removing Na or adding amiloride (10−4
m). When, after the action of ouabain, Na was removed from the outside bathing solution, the Na and K concentration in all layers returned to control values. The latter effect could be abolished by amiloride. The other cell types of the epithelium showed under some experimental conditions a different behavior. In the cornified cells and the light cells, which occurred occasionally in the stratum granulosum, the electrolyte concentrations approximated those of the outer bathing meium under all experimental conditions. In the mitochondria-rich cells, the Na influx after ouabain could not be, prevented by adding amiloride. In the gland cells, only a small change in the Na and K concentrations could be detected after ouabain. The results of the present study are consistent with a two-barrier concept of transepithelial Na transport. The Na transport compartment comprises all living epithelial layers. Therefore, with the exception of some epithelial cell types, the frog skin epithelium can be regarded as a functional syncytium for Na.

Electron microprobe analysis of frog skin epithelium: evidence for a syncytial sodium transport compartment.

A micropipette technique was used to induce local changes of the bicarbonate concentration of the cerebro-spinal fluid surrounding arterioles on the exposed cerebral cortex of anaesthetized rats and cats. Injection volumes of a few nanoliters caused circumscribed and pronounced changes of the diameter of the arterioles under study: mock spinal fluid without bicarbonate dilated, while a solution containing 25 meq/l of bicarbonate constricted the vessels. In such experiments the localpCO2 of the arteriolar wall remains practically constant, since it is set by thepCO2 of the arterial blood and of the cerebral tissue. Hence the microinjections essentially consisted in a local change of the pH of the fluid surrounding a small segment of a cerebral arteriole. Since metabolic changes of the nervous tissue changes the periarteriolar pH, it is probable that local pH induced vasomotor changes of the type reported here participate in the so called metabolic regulation of the cerebral blood flow which underlies the local adaptation of the cerebral blood flow to changing functional demands.

Micropuncture evaluation of the importance of perivascular pH for the arteriolar diameter on the brain surface

[Hemodynamics of kidney medullary substance. Part I. Capillary passage time, blood volume, circulation, tissue hematocrit and oxygen consumption of kidney medullary substance in situ].

Klaus Thurau

Papers

Perivascular Potassium and pH as Determinants of Local Pial Arterial Diameter in Cats A MICROAPPLICATION STUDY

Micropuncture studies on the filtration rate of single superficial and juxtamedullary glomeruli in the rat kidney.

Electron microprobe analysis of frog skin epithelium: evidence for a syncytial sodium transport compartment.

Micropuncture evaluation of the importance of perivascular pH for the arteriolar diameter on the brain surface

[Hemodynamics of kidney medullary substance. Part I. Capillary passage time, blood volume, circulation, tissue hematocrit and oxygen consumption of kidney medullary substance in situ].