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S N Orlov

Publications and source records attributed to S N Orlov.

At least 55 records · Page 3Linked to original sources
PubMed1996

Bumetanide-sensitive ion fluxes in vascular smooth muscle cells: lack of functional Na+, K+, 2 Cl- cotransport.

To examine the involvement of Na+,K+,2Cl- cotransport in monovalent ion fluxes in vascular smooth muscle cells (VSMC), we compared the effect of bumetanide on 86Rb, 36Cl and 22Na uptake by quiescent cultures of VSMC from rat aorta. Under basal conditions, the values of bumetanide-sensitive (BS) inward and outward 86Rb fluxes were not different. Bumetanide decreased basal 86Rb uptake by 70-75% with a Ki of approximately 0.2-0.3 microM. At concentrations ranging up to 1 microM, bumetanide did not affect 36Cl influx and reduced it by 20-30% in the range from 3 to 100 microM. In contrast to 86Rb and 36Cl influx, bumetanide did not inhibit 22Na uptake by VSMC. BS 86Rb uptake was completely abolished in Na(+)- or Cl(-)-free media. In contrast to 86Rb, basal BS 36Cl influx was not affected by Nao+ and Ko+. Hyperosmotic and isosmotic shrinkage of VSMC increased 86Rb and 36Cl influx to the same extent. Shrinkage-induced increments of 86Rb and 36Cl uptake were completely abolished by bumetanide with a Ki or approximately 0.3 microM. Shrinkage did not induce BS 86Rb and 36Cl influx in (Na+ or Cl-)- and (Na+ or K+)-depleted media, respectively. In the presence of an inhibitor of Na+/H+ exchange (EIPA), neither hyperosmotic nor isosmotic shrinkage activated 22Na influx. Bumetanide (1 microM) did not modify basal VSMC volume and intracellular content of sodium, potassium and chloride but abolished the regulatory volume increase in isosmotically-shrunken VSMC. These data demonstrate the absence of the functional Na+,K+,2Cl- cotransporter in VSMC and suggest that in these cells basal and shrinkage-induced BS K+ influx is mediated by (Nao+ + Clo-)-dependent K+/K+ exchange and Nao(+)-dependent K+,Cl- cotransport, respectively.

Animals↗
PubMed1996

Cell volume in vascular smooth muscle is regulated by bumetanide-sensitive ion transport.

Vascular smooth muscle cells (VSMC) exhibit shrinkage-induced bumetanide-inhibited 86Rb influx and ethylisopropylamiloride (EIPA)-inhibited 22Na influx. In this study, we examined the role of these transport pathways in volume adjustment of VSMC after isosmotic and hyperosmotic shrinkage. Cell volume was assessed by measurement of [14C]urea distribution. An initial 18-20% cell volume decrease in isosmotically shrunken VSMC was followed by a regulatory volume increase (RVI). RVI was completely abolished by bumetanide but not by EIPA. No RVI was noted in hyperosmotically shrunken VSMC. The initial rate of bumetanide-inhibited 86Rb influx was two- to threefold higher in isosmotically shrunken VSMC than with hyperosmotic shrinkage. Hyperosmotic shrinkage of VSMC was accompanied by a three- to fourfold increase in the rate of bumetanide-inhibited 86Rb efflux, whereas isosmotic shrinkage augmented this component by only 20-30%. In contrast to bumetanide-inhibited 86Rb influx, isosmotic shrinkage slightly increased the rate of EIPA-sensitive 22Na influx. Hyperosmotic shrinkage led to transient activation of EIPA-inhibited 22Na influx, which was completely abolished in 15 min. Activation of adenosine 3',5'-cyclic monophosphate (cAMP) signaling with isoproterenol arborized VSMC and decreased their volume by approximately 15%. A similar volume decrease was seen in VSMC treated with the microfilament-disrupting compound, cytochalasin B. The isoproterenol-induced cell volume decrease was prolonged by the addition of bumetanide. Unlike isoproterenol, agents that raise intracellular Ca2+ (A-23187 and angiotensin II) did not modify VSMC volume. Thus our data demonstrate involvement of cAMP signaling in the regulating of VSMC volume and a key role of bumetanide-inhibited ion transport in the RVI after isosmotically induced shrinkage.

Animals↗
PubMed1996

cAMP signaling inhibits dihydropyridine-sensitive Ca2+ influx in vascular smooth muscle cells.

This study examines the role of the cAMP signaling pathway in the regulation of 45Ca influx in cultured vascular smooth muscle cells from the rat aorta. K+o-induced depolarization of smooth muscle cells increased the rate of 45Ca uptake by twofold to threefold. This effect was completely abolished by the dihydropyridine derivatives nifedipine and nicardipine, with a Ki of 3 and 10 nmol/L, respectively. Activators of cAMP signaling (isoproterenol, forskolin, cholera toxin) increased cAMP content by 50- to 100-fold and decreased voltage-dependent 45Ca uptake by 50% to 70%. Neither the dihydropyridines nor the cAMP activators affected basal 45Ca influx. Direct addition of the protein kinase inhibitor H-89 to the incubation medium in the 1- to 10-micromol/L range did not alter basal 45Ca uptake but completely abolished voltage-dependent Ca2+ transport. Preincubation of cells for 1 hour with 10 micromol/L H-89 did not modify basal and depolarization-induced 45Ca uptake in H-89-free medium but prevented forskolin-induced inhibition of voltage-dependent Ca2+ influx. The addition of cytoskeleton-active compounds reduced voltage-dependent Ca2+ transport and completely abolished its regulation by cAMP. Activation of cAMP signaling decreased the volume of smooth muscle cells by 12% to 15%. The same cell volume diminution in hyperosmotic medium did not alter voltage-dependent 45Ca uptake. Thus, data obtained in this study show that in contrast to cardiac and skeletal myocytes, in vascular smooth muscle cells, 45Ca influx, putatively due to L-type channels, is inhibited by cAMP. This regulatory pathway appears to be mediated via protein kinase A activation and cytoskeleton reorganization.

Animals↗
PubMed1996

Apoptosis and vascular wall remodeling in hypertension.

Vascular structure plays a key role in the pathogenesis of hypertension. Because it is less readily reversible than protein accumulation, DNA accumulation in the arterial wall may be considered as a record of past episodes of vascular growth, contributing to the persistence of the vascular disease. Apoptosis, a ubiquitous and highly regulated form of programmed cell death that is involved in tissue morphogenesis and homeostasis as the essential counterpart of cell replication, is potentially involved in the regulation of vascular structure, via the deletion of cells in the vessel wall. We discuss how the current knowledge on apoptosis may provide insights into the pathogenesis of vascular wall remodeling, with an emphasis on the biology of vascular smooth muscle cells. Evidence suggests that heightened cell replication rates are often associated with increased apoptosis, as for smooth muscle cells in genetic hypertension or in arterial repair after injury. However, apoptotic cell death may also be regulated independently of cell growth. The triggering of apoptosis depends on a balance of environmental cues that are not specific to apoptosis. However, there is a common set of key biochemical events mediating apoptosis (i.e., committing the cell to die), thus providing a basis for the design of novel pharmacological strategies specifically targeting apoptotic cell death. The identification of biochemical markers of apoptosis and other methodological advances will ultimately help in understanding the role of apoptotic cell death in vascular remodeling and hypertensive end-organ damage.

Animals↗
PubMed1996

The time window of apoptosis: a new component in the therapeutic strategy for cardiovascular remodeling.

APOPTOSIS AND EXPERIMENTAL HYPERTROPHY: Apoptosis (programmed cell death) is a physiological counterpart of cell replication with shared as well as specific pathways. Our initial studies have demonstrated increased apoptosis in the heart, kidney and brain of spontaneously hypertensive rats (SHR) and mice, persisting in cultured vascular smooth muscle cells. In these target organs of hypertension, programmed cell death paralleled the well known hypertrophy/hyperplasia. We also observed that the two processes can be dissociated in time, as in experimental hypertrophy of the heart induced by pressure overload. In this context, only a short-lived apoptotic window precedes the overt development of cardiac hypertrophy. EFFECTS IN HYPERTENSION: We now propose that a more prolonged apoptotic window is present in hypertension. Apoptosis seems to be significantly reduced during the first weeks of life in SHR, possibly contributing to the early cardiac hyperplasia. However, increased apoptosis is clearly evident thereafter throughout the development of hypertension and fades below the levels observed in normotensive animals after the age of 24 weeks. ANTIHYPERTENSIVE THERAPY AND APOPTOSIS: In addition to the apoptotic windows that suggest a dynamic regulation of this process in disease states, antihypertensive therapy with angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists and calcium channel blockers can also modify the contribution of apoptosis, independently of the blood pressure fall. We propose that the presence of apoptotic windows and the involvement of this biological process as a primary or secondary event in cardiovascular remodeling should be taken into account when designing innovative therapeutic approaches.

Animals↗
PubMed1995

Inward potassium transport systems in skeletal muscle derived cells are highly sensitive to oxidant exposure.

Strenuous physical exercise causes a remarkable perturbation of K+ homeostasis in skeletal muscle tissue. Potassium efflux is crucial for a number of physiological control processes; however, exercise-induced perturbation of K+ homeostasis in skeletal muscle is suggested to be implicated in the generation of muscle fatigue. Physical exercise is also known to induce oxidative stress; a possible contribution of oxygen free radicals to the development of muscle fatigue has been hypothesized. To reveal the dose-dependent effect of oxidant exposure on inward and outward K+ (86RbCl) transporting systems, skeletal muscle derived L6 cells were treated with different concentrations of tert-butylhydroperoxide (TBOOH). We document the responses of (1) the ouabain-sensitive component of K+ influx (Na+,K+ pump), (2) bumetanide-sensitive ouabain-insensitive component of K+ influx (Na+,K+, 2Cl- cotransporter), (3) ouabain- and bumetanide-insensitive component of K+ influx (passive permeability of the cell membrane to inward K+), (4) ouabain-insensitive component of K+ efflux, and (5) passive leakage component of K+ efflux following exposure of L6 cells to oxidant treatment. Even very low doses of TBOOH (25 mumol) caused powerful activation of the Na+,K+ pump. Following TBOOH treatment, activity of the Na+,K+,2Cl- cotransporter was remarkably inhibited. Such a treatment also significantly decreased the permeability of the cell membrane to inward flux of K+ (passive influx). Thus, we observed that even very low doses of oxidant had remarkable specific effects on the different components of K+ influx in the skeletal muscle derived cells. However, K+ efflux mechanisms appeared to be rather insensitive to the extracellular oxidant challenge.

Dose-Response Relationship, Drug↗
PubMed1995

Altered beta-adrenergic regulation of Na-K-Cl cotransport in cultured smooth muscle cells from the aorta of spontaneously hypertensive rats. Role of the cytoskeleton network.

To verify the hypothesis of Na-K-Cl cotransport (COTR) involvement in ion transport abnormalities as revealed in vascular smooth muscle cells (VSMC) of spontaneously hypertensive rats (SHR), we compared the rate of ouabain-insensitive, bumetanide-inhibited 86Rb influx in quiescent and growing cultures of VSMC from the aorta of SHR and normotensive (BN.lx) rats and its regulation by the cAMP signaling system. Basal COTR was not altered in quiescent cells from SHR but was decreased by 30% to 40% (P < .02) in growing SHR VSMC as compared to BN.lx rats. In quiescent BN.lx VSMC, isoproterenol inhibited COTR by 50% and induced cell shape transition of > 90% of cells, resulting in the appearance of rounded VSMC with arborized cytoplasms. In contrast, isoproterenol elicited cell shape transition in only 50% of quiescent SHR VSMC and did not modify COTR. In growing cells, it decreased COTR by 85% to 95% and altered cell morphology in > 95% of VSMC without differences between SHR and BN.lx rats. Neither inhibitors of protein kinase A (H-89 and KT-5720) nor an inhibitor of phosphoprotein phosphatase (okadaic acid) affected cell shape transition and COTR suppression in isoproterenol-treated VSMC. The COTR suppression and cytoplasm arborization was also demonstrated by the addition of cytochalasin B, a disintegrator of microfilament bundles, and staurosporine, an inhibitor of protein kinase C. The effects of these compounds on COTR and SHR and BN.lx VSMC morphology were not different. The calmodulin antagonist R24571 decreased COTR by 60% to 70% in quiescent BN.lx VSMC and did not modify this carrier in SHR VSMC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1995

Unidirectional sodium and potassium flux in myogenic L6 cells: mechanisms and volume-dependent regulation.

To clarify the relative participation of particular ion transport systems in net univalent cation fluxes under basal conditions and altered volume of skeletal muscle-derived cells, the effect of inhibitors of the Na(+)-K+ pump (ouabain), univalent ion cotransporters [bumetanide, furosemide, and (dihydroindenyl)oxy alkanoic acid], and N+/H+ exchanger (ethylisopropylamiloride) on 86Rb and 22Na fluxes has been studied in L6 myoblasts incubated in isosmotic (320 mosmol/kg) and anisosmotic media. Under the isosmotic condition, the relative contribution of ouabain-inhibited and ouabain-insensitive bumetanide-inhibited component of 86Rb influx was approximately 15-20 and 60%, respectively. 22Na influx was inhibited by bumetanide and ethylisopropylamiloride by 25 and 15%, respectively. Under isosmotic conditions, an increase of L6 cell volume was observed after addition of extracellular acetylcholine, extracellular K(+)-induced depolarization, or lowering of the pH of the incubation medium. High extracellular glutathione (150 microM) did not affect the cell volume of the muscle-derived cells bathed in isosmotic medium. Results of this study suggest that the bumetanide-inhibited component of K+ influx plays a key role in the adjustment of transmembrane K+ gradient in L6 myoblasts. The Na+/H+ exchanger appears to be important in regulatory volume increase.

Acetylcholine↗
PubMed1995

Apoptosis in target organs of hypertension.

Apoptosis or programmed cell death frequently parallels abnormalities in cell proliferation and differentiation. As hypertrophy/hyperplasia or remodeling occurs in organs affected by hypertension, we evaluated the degree of apoptosis in the heart, kidney, and brain in situ in genetically hypertensive mice and rats as well as in cultured vascular smooth muscle cells. Apoptosis was characterized by morphological features, DNA fragmentation, and laddering as well as by terminal deoxynucleotidyl transferase labeling of the 3' OH ends of both extracted DNA and tissue sections. The present report provides the first evidence of increased apoptosis in whole organs of genetically hypertensive rat and mouse strains: in the heart of spontaneously hypertensive rats (SHR) and in the heart (ventricular cardiomyocytes), kidney (inner cortex and medulla), and brain (cortex, striatum, hippocampus, and thalamus) of spontaneously hypertensive mice, with a higher effect of apoptotic inducers in cultured aortic smooth muscle cells derived from SHR. Both types of known apoptotic processes, oligonucleosomal cleavage and large DNA fragmentation, were observed in vascular smooth muscle cells, but only the former appeared to be increased in SHR. This study underlines the importance of cell death dysregulation in hypertension, reveals a new route for investigation of the pathogenesis of hypertension, and suggests novel targets of therapeutic intervention.

Animals↗
PubMed1995

Genes of intracellular calcium metabolism and blood pressure control in primary hypertension.

In the last two decades, major progress has been made in understanding the role of calcium (Ca) metabolism in blood pressure (BP) control. This article discusses the intracellular Ca handling systems that could potentially be involved in the pathogenesis of primary hypertension. We begin by reviewing our current knowledge of intracellular Ca handling, alterations of intracellular Ca metabolism in primary hypertension, and possible mechanisms of BP control. We have analyzed data on the structure and alternative splicing of major genes controlling intracellular free Ca concentration, ie, genes encoding intracellular Ca-binding protein (calmodulin, calbindin, plasma membrane Ca2+ pump, Na+/Ca2+ exchanger, and voltage-dependent Ca channels). Data are presented on the relationship of gene polymorphism and alternative splicing with membrane architecture and the function of gene products. Numerous observations on abnormalities of these gene products in primary hypertension are summarized. Studies on the polymorphism of genes regulating intracellular Ca in hypertension are only now being performed.

Animals↗
PubMed1994

Swelling-induced K+ influx in cultured primary astrocytes.

The effect of swelling of cultured primary astrocytes from rat brain in hypotonic medium on K+ influx has been studied. A decrease in osmolality from 310 to 180 mOsm increased the activity of sodium pump (ouabain-inhibited 86Rb+ influx) and Na+,K+,2Cl- cotransport (ouabain-insensitive bumetanide-inhibited 86Rb+ influx) by 70 and 35%, respectively. It is suggested that activation of these transport systems makes it possible to retain a high potassium concentration in the cells under regulatory volume decrease.

Animals↗
PubMed1994

Osmotic regulation of sodium pump in rat brain synaptosomes: the role of cytoplasmic sodium.

The effect of hypoosmolality of incubation medium on the rat of ouabain-sensitive 86Rb+ transport in rat brain synaptosomes was studied. A decreased osmolality from 310 to 250 mOsm increased the rate of 86Rb+ uptake from 3.72 to 6.23 nmol/mg of protein min. To evaluate the involvement of cytoplasmic sodium in sodium pump stimulation inhibitors of ion channels and transport pathways able to increase [Na+]in were used. Tetrodotoxin (1 microM), amiloride (0.5 mM) and verapamil (0.1 mM) had no influence on the osmotic response of the sodium pump. The decrease of sodium concentration in incubation medium to 15 mM, leading to a practical loss of its transmembrane gradient, did not abolish stimulation of pump. No increase in 22Na+ influx or intrasynaptosomal sodium content was registered at hypotonic conditions. It is suggested that osmotic regulation of Na+,K(+)-ATPase is not connected with an increase of internal sodium through opening of sodium channels, or with activation of other membrane sodium-transporting systems.

Animals↗
PubMed1994

Univalent cation fluxes in human erythrocytes from individuals with low or normal sodium intake.

BACKGROUND: High salt intake is a risk factor for essential hypertension in man. There is evidence that, in hypertension, intracellular sodium content and univalent cation transport across erythrocyte membranes are changed. It has been proposed that a low-sodium diet has an antihypertensive effect; this may be related to changes in cation fluxes across plasma membranes. METHODS: Sodium and potassium fluxes and the composition of fatty acids were studied in the erythrocytes of people who had eaten a low-sodium vegan diet for many years (n = 9) and in those of controls who had consumed a mixed diet (n = 11) to investigate the dependence of these variables on dietary factors. Both systolic and diastolic blood pressures were lower in vegans than in controls. RESULTS: The passive permeability to sodium (P < 0.05) ,Na+,K+ cotransport (P < .001) and the intracellular content of exchangeable sodium (P = 0.076) were decreased in the erythrocytes of those who had consumed the low-sodium diet compared with the controls. The activity of the Na+-K+ pump, Na+-H+ exchange and the passive permeability to potassium were unaltered. Swelling-induced K+,C1- cotransport was increased in the erythrocytes of those who had eaten the low-sodium vegan diet compared with controls (P < 0.01). The proportion of linoleic acid was increased (P < 0.01) at the expense of eicosapentaenoic and docosahexaenoic acids (P < 0.001) in the erythrocyte membranes of the vegans. CONCLUSION: Our results show that levels of intracellular sodium and Na+,K+ cotransport activity, which increase in patients with hypertension, decreased in those consuming a low-sodium vegan diet. This suggests that the risk of essential hypertension was diminished in the vegan participants, confirming our observation that systolic and diastolic blood pressures were lower in the strict vegans than in the controls.

Adult↗
PubMed1994

[The role of phospholipase A2, 5-lipoxygenase, and cyclooxygenase in activation of human neutrophil "oxygen burst": the modulating effect of osmolality of the medium].

The roles of phospholipase A2, 5-lipoxygenase and cyclooxygenase in activation of "oxidative burst" in human neutrophils have been studied under isoosmotic (320 mOsM), hypoosmotic (200 mOsM) and hyperosmotic (420 mOsM) conditions. The oxidative burst induced by phorbol-12-myristate-13-acetate (PMA), calcium ionophore A23187 and opsonized zymosan was followed by luminol-dependent chemiluminescence (CL). There were no differences in the concentration dependences of CL inhibition at 320 mOsM and 200 mOsM in the presence of the phospholipase A2 inhibitor, p-bromphenacylbromide. Contrariwise, at 420 mOsM the sensitivity to inhibition was decreased by PMA and A23187 but increased by opsonized zymosan. A change in the medium osmolality in the presence of the 5-lipoxygenase inhibitor quercetin did not result in the modification of the concentration dependence of CL inhibition induced by any of the activators. In the presence of the cyclooxygenase inhibitor, meclofenamic acid, the "oxidative burst" induced by PMA and A23187 at 200 mOsM was manifested as a decrease of the sensitivity to inhibition, while at 420 mOsM this sensitivity was increased in comparison with that observed under isoosmotic conditions. The data obtained suggest that phospholipase A2 and cyclooxygenase play a role in the mechanism of the modulating effect of the medium osmolality on the "oxidative burst" in neutrophils, while 5-lipoxygenase is unimportant for this process.

Acetophenones↗
PubMed1994

[Na+/H+- and Na+/Na+-countertransport in human, rabbit, and rat erythrocytes: evidence for the existence of two independent ion-transporting systems].

The activity and regulatory features of the Na+/H(+)- and Na+/Na(+)-exchange were studied in human, rabbit and rat red blood cells. No basal activity of the Na+/H(+)-exchange (the amyloride-inhibited component of the 22Na+ influx) in erythrocytes of these species was observed. The rate of 22Na+ influx increased rapidly when the experiments were carried out on acid-loaded cells in an alkaline (pH0 = 8.0) incubation medium (delta mu H(+)-induced Na+/H(+)-exchange). The ratio of delta mu H(+)-induced Na+/H(+)-exchange activities in human, rabbit and rat red blood cells was 1.0 : 1.1 : 2.3, respectively, whereas that of the Na+/Na(+)-exchange activities (the phloretin-inhibited component of the 22Na+ influx) in erythrocytes of these species was 1.0 : 4.6 : 0.2. The osmotic shrinkage of rat and rabbit erythrocytes led to the stimulation of the Na+/H(+)- (but not Na+/Na+) exchange. Amyloride (1 mM) inhibited the shrinkage-induced 22Na+ entry as well as the delta mu H(+)-induced 22Na+ entry--by 95 and 10-20%, respectively. Heat treatment (10 min, 49-51 degrees C), disturbing the membrane cytoskeleton suppressed both the shrinkage-induced activation and the delta mu H(+)-induced activation of the Na+/H(+)-exchange. The data obtained indicate that the both transport systems are mediated by two distinct transport carriers. It may be suggested that the delta mu H(+)-induced Na+/H(+)-exchange, on the one hand, and the shrinkage-induced Na+/H(+)-exchange, on the other, are mediated by two different Na+/H(+)-exchanger subtypes.

Amiloride↗
PubMed1993

Volume-dependent regulation of the respiratory burst of activated human neutrophils.

The effect of incubation medium osmolality on the respiratory burst of human neutrophils was studied using luminol-dependent chemiluminescence (CL) as an indicator of burst activity. Neutrophils were stimulated with N-formyl-Met-Leu-Phe (FMLP), phorbol-12-myristate-13-acetate (PMA), the calcium ionophore A23187, thermoaggregated IgG (IgGn), and opsonized zymosan (OZ). It was shown that increasing the osmolality of the incubation medium from 320 up to 420 mosM decreased the A23187- and OZ-induced CL responses by 90%. Under the same conditions PMA-, FMLP- and IgGn-induced CL responses were decreased by 40-60%. A decrease of osmolality to 200 mosM resulted in a 2-3 fold decrease of the A23187-, PMA- and FMLP-induced CL and in a 60-80% increase of OZ- and IgGn-induced CL. It is suggested that osmolality-mediated alteration of cell volume is an important mechanism for regulating neutrophil activity.

Adult↗
PubMed1993

Kinetics and peculiarities of thermal inactivation of volume-induced Na+/H+ exchange, Na+,K+,2Cl- cotransport and K+,Cl- cotransport in rat erythrocytes.

The kinetics of the volume-dependent activation of Na+/H+ exchange, Na+,K+,2Cl(-)-cotransport and K+,Cl(-)-cotransport in rat erythrocytes was studied. The significant increase in the rate of Na+/H+ exchange is observed within 15 min after hypertonic shrinkage while the maximum transport rate is reached by 20 min. A delay of about 5 min was found in activation of Na+,K+,2Cl(-)-cotransport, the maximum transport rate being reached 10 min after shrinkage. Activation of K+,Cl(-)-cotransport by hypotonic swelling was registered within 10 min after cell swelling, with a simultaneous achievement of the constant transport rate. Preincubation of cells at 49 degrees C has no effect on the basal Na+/H+ exchange and Na+,K+,2Cl(-)-cotransport but suppresses the activation of these systems by osmotic shrinkage. On the contrary, the rate of K+,Cl(-)-cotransport in isosmotic medium is raised 10-fold after preincubation at 49 degrees C. The thermal treatment at 49 degrees C blocks the activation of K+,Cl(-)-cotransport by swelling. On the basis of the data on thermal denaturation of spectrin at the same temperature it was suggested that the cytoskeleton of erythrocyte membrane is involved in volume regulation of the ion-transporting systems and that the molecular mechanisms which underlie the activation of Na+/H+ exchange, Na+,K+,2Cl(-)-cotransport and K+,Cl(-)-cotransport are essentially different.

Animals↗