scholarly journals Ionic Mechanisms of Cardiac Cell Swelling Induced by Blocking Na+/K+ Pump As Revealed by Experiments and Simulation

2006 ◽  
Vol 128 (5) ◽  
pp. 495-507 ◽  
Author(s):  
Ayako Takeuchi ◽  
Shuji Tatsumi ◽  
Nobuaki Sarai ◽  
Keisuke Terashima ◽  
Satoshi Matsuoka ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Cell Volume ◽  
Ventricular Myocytes ◽  
Cell Model ◽  
Drug Application ◽  
Membrane Depolarization ◽  
Cell Swelling ◽  
Cardiac Cell ◽  
Ionic Mechanisms ◽  
Ca2 Channels

Although the Na+/K+ pump is one of the key mechanisms responsible for maintaining cell volume, we have observed experimentally that cell volume remained almost constant during 90 min exposure of guinea pig ventricular myocytes to ouabain. Simulation of this finding using a comprehensive cardiac cell model (Kyoto model incorporating Cl− and water fluxes) predicted roles for the plasma membrane Ca2+-ATPase (PMCA) and Na+/Ca2+ exchanger, in addition to low membrane permeabilities for Na+ and Cl−, in maintaining cell volume. PMCA might help maintain the [Ca2+] gradient across the membrane though compromised, and thereby promote reverse Na+/Ca2+ exchange stimulated by the increased [Na+]i as well as the membrane depolarization. Na+ extrusion via Na+/Ca2+ exchange delayed cell swelling during Na+/K+ pump block. Supporting these model predictions, we observed ventricular cell swelling after blocking Na+/Ca2+ exchange with KB-R7943 or SEA0400 in the presence of ouabain. When Cl− conductance via the cystic fibrosis transmembrane conductance regulator (CFTR) was activated with isoproterenol during the ouabain treatment, cells showed an initial shrinkage to 94.2 ± 0.5%, followed by a marked swelling 52.0 ± 4.9 min after drug application. Concomitantly with the onset of swelling, a rapid jump of membrane potential was observed. These experimental observations could be reproduced well by the model simulations. Namely, the Cl− efflux via CFTR accompanied by a concomitant cation efflux caused the initial volume decrease. Then, the gradual membrane depolarization induced by the Na+/K+ pump block activated the window current of the L-type Ca2+ current, which increased [Ca2+]i. Finally, the activation of Ca2+-dependent cation conductance induced the jump of membrane potential, and the rapid accumulation of intracellular Na+ accompanied by the Cl− influx via CFTR, resulting in the cell swelling. The pivotal role of L-type Ca2+ channels predicted in the simulation was demonstrated in experiments, where blocking Ca2+ channels resulted in a much delayed cell swelling.

Effect of isosmotic removal of extracellular Ca2+ and of membrane potential on cell volume in muscle cells

1994 ◽  
Vol 267 (3) ◽  
pp. C768-C775 ◽  
Author(s):  
C. Pena-Rasgado ◽  
K. D. McGruder ◽  
J. C. Summers ◽  
H. Rasgado-Flores
Keyword(s):  
Membrane Potential ◽  
Sarcoplasmic Reticulum ◽  
Cell Volume ◽  
Muscle Cells ◽  
Membrane Depolarization ◽  
Volume Reduction ◽  
Sensitive Volume ◽  
Volume Increase ◽  
Dependent Cell ◽  
In Cells

Isosmotic removal of extracellular Ca2+ (Cao) and changes in membrane potential (Vm) are frequently performed manipulations. Using isolated voltage-clamped barnacle muscle cells, we studied the effect of these manipulations on isosmotic cell volume. Replacing Cao by Mg2+ induced 1) verapamil-sensitive extracellular Na(+)-dependent membrane depolarization, 2) membrane depolarization-dependent cell volume reduction in cells whose sarcoplasmic reticulum (SR) was presumably loaded with Ca2+ [intracellular Ca2+ (Cai)-loaded cells], and 3) cell volume increase in cells whose SR was presumably depleted of Ca2+ (Cai-depleted cells) or in Cai-loaded cells whose Vm was held constant. Membrane depolarization induced 1) volume reduction in Cai-loaded cells or 2) verapamil-sensitive volume increase in Cai-depleted cells. This suggests tha, in Cai-loaded cells, membrane depolarization induces SR Ca2+ release, which in turn promotes volume reduction. Conversely, in Cai-depleted cells, the depolarization activates Na+ influx through a verapamil-sensitive pathway leading to the volume increase. This pathway is also revealed when Cao is removed in either Cai-depleted cells or in cells whose Vm is held constant.

Stretch- and volume-activated channels in isolated proximal tubule cells

1992 ◽  
Vol 262 (5) ◽  
pp. F857-F870 ◽  
Author(s):  
D. Filipovic ◽  
H. Sackin
Keyword(s):  
Membrane Potential ◽  
Proximal Tubule ◽  
Cell Volume ◽  
Regulatory Volume Decrease ◽  
Cell Swelling ◽  
Isolated Cells ◽  
Open Probability ◽  
Proximal Tubule Cells ◽  
Open Time ◽  
Tubule Cells

Apical and basolateral channels were studied in isolated proximal tubule cells of Necturus kidney. Many of these isolated cells maintained their polarity, with clearly delineated apical and basolateral regions. A 20-pS stretch-activated (SA) cation-selective channel was identified at the apical side of these cells. This channel was permeable to Ca, K, and Na but was not significantly gated by either membrane potential or cytosolic Ca. Negative pipette pressure (15 cmH2O) increased the open probability (Po) of this channel from 0.04 +/- 0.02 to 0.26 +/- 0.08 (n = 6). Two types of Ca-independent, mechanosensitive, K-selective (SAK) channels were identified at the basolateral surface of polarized proximal tubule cells, i.e., a 30-pS long-open time (50 +/- 7 ms) channel (n = 9), and a 46-pS short-open time (1.3 +/- 0.7 ms) channel (n = 10). Pipette suction (-12 cmH2O) increased the Po of the short-open time channels from 0.008 to 0.015 and increased the Po of the long-open time channel from 0.03 to 0.19. The effect of swelling was studied with isolated cells suspended at the tip of patch pipettes. A 50% dilution of the bath doubled cell volume, hyperpolarized the membrane potential by 11 +/- 0.7 mV, and increased the Po of the basolateral SAK channels. This was followed by a spontaneous regulatory volume decrease (RVD), repolarization of the membrane potential, and a decrease in Po. In contrast, isosmotic (bath side) replacement of an impermeant anion (methanesulfonate) with a permeant anion (Cl) doubled cell volume in 5 min but without a subsequent RVD. This sustained swelling hyperpolarized the cell potential by 5.5 +/- 0.7 mV (n = 16) and increased the Po of short-open time channel by a factor of 2.3 from 0.03 +/- 0.01 to 0.07 +/- 0.02 (n = 6). The increase in Po was primarily produced by a reduction in the interburst closed time, which decreased from 142 +/- 43 ms in K methanesulfonate to 36 +/- 11 ms in KCl solutions. These results are consistent with the hypothesis that cell swelling activates Ca-independent K channels at the basolateral membrane of renal proximal tubule. Efflux of K through these channels may partially mediate renal cell volume regulation.

scholarly journals Anion transport in dog, cat, and human red cells. Effects of varying cell volume and Donnan ratio.

1979 ◽  
Vol 74 (3) ◽  
pp. 319-334 ◽  
Author(s):  
V Castranova ◽  
M J Weise ◽  
J F Hoffman
Keyword(s):  
Membrane Potential ◽  
Cell Volume ◽  
Rate Constant ◽  
Rate Constants ◽  
Anion Transport ◽  
Atp Depletion ◽  
Red Cells ◽  
Cell Swelling ◽  
Equilibrium Ratio ◽  
Human Red Cells

Membrane potential and the rate constants for anion self-exchange in dog, cat, and human red blood cells have been shown to vary with cell volume. For dog and cat red cells, the outward rate constants for SO4 and Cl increase while the inward rate constant for SO4 decreases as cells swell or shrink. These changes coincide with the membrane potential becoming more negative as a result of changes in cell volume. Human red cells exhibit a similar change in the rate constants for SO4 and Cl efflux in response to cell swelling, but shrunken cells exhibit a decreased rate constant for SO4 efflux and a more positive membrane potential. Hyperpolarization of shrunken dog and cat red cells is due to a volume-dependent rate constant for SO4 efflux and a more positive membrane potential. Hyperpolarization of shrunken dog and cat red cells is due to a volume-dependent increase in PNa. If this increase in PNa is prevented by ATP depletion or if the outward Na gradient is removed, the response to shrinking is identical to human red cells. These results suggest that the volume dependence of anion permeability may be secondary to changes in the anion equilibrium ratio which in red cells is reflected by the membrane potential. When the membrane potential and cell volume of human red cells were varied independently by a method involving pretreatment with nystatin, it was found that the rate of anion transport (for SO4 and Cl) does not vary with cell volume but rather with membrane potential (anion equilibrium ratio); that is, the rate constant for anion efflux is decreased and that for influx is increased as the membrane potential becomes more positive (internal anion concentration increases) while the opposite is true with membrane hyperpolarization (a fall in internal anion concentration).

scholarly journals Glycine Induces Migration of Microglial BV-2 Cells via SNAT-Mediated Cell Swelling

2018 ◽  
Vol 50 (4) ◽  
pp. 1460-1473 ◽  
Author(s):  
Michael Kittl ◽  
Heidemarie Dobias ◽  
Marlena Beyreis ◽  
Tobias Kiesslich ◽  
Christian Mayr ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Membrane Potential ◽  
Amino Acid ◽  
Cell Membrane ◽  
Cell Volume ◽  
Cell Membrane Potential ◽  
Microglial Cells ◽  
Cell Swelling ◽  
Electrophysiological Recordings ◽  
A Cell

Background/Aims: The neutral, non-essential amino acid glycine has manifold functions and effects under physiological and pathophysiological conditions. Besides its function as a neurotransmitter in the central nervous system, glycine also exerts immunomodulatory effects and as an osmolyte it participates in cell volume regulation. During phagocytosis, glycine contributes to (local) cell volume-dependent processes like lamellipodium formation. Similar to the expansion of the lamellipodium we assume that glycine also affects the migration of microglial cells in a cell volume-dependent manner. Methods: Mean cell volume (MCV) and cell migration were determined using flow cytometry and trans-well migration assays, respectively. Electrophysiological recordings of the cell membrane potential (Vmem) and swelling-dependent chloride (Cl-) currents (IClswell, VSOR, VRAC) were performed using the whole-cell patch clamp technique. Results: In the murine microglial cell line BV-2, flow cytometry analysis revealed that glycine (5 mM) increases the MCV by ∼9%. The glycine-dependent increase in MCV was suppressed by the partial sodium-dependent neutral amino acid transporter (SNAT) antagonist MeAIB and augmented by the Cl- current blocker DCPIB. Electrophysiological recordings showed that addition of glycine activates a Cl- current under isotonic conditions resembling features of the swelling-activated Cl- current (IClswell). The cell membrane potential (Vmem) displayed a distinctive time course after glycine application; initially, glycine evoked a rapid depolarization mediated by Na+-coupled glycine uptake via SNAT, followed by a further gradual depolarization, which was fully suppressed by DCPIB. Interestingly, glycine significantly increased migration of BV-2 cells, which was suppressed by MeAIB, suggesting that SNAT is involved in the migration process of microglial cells. Conclusion: We conclude that glycine acts as a chemoattractant for microglial cells presumably by a cell volume-dependent mechanism involving SNAT-mediated cell swelling.

Voltage-dependent effects of isoproterenol on cytosolic Ca concentration in rat heart

1987 ◽  
Vol 252 (4) ◽  
pp. H697-H703 ◽  
Author(s):  
S. S. Sheu ◽  
V. K. Sharma ◽  
M. Korth
Keyword(s):  
Membrane Potential ◽  
Calcium Concentration ◽  
Ventricular Myocytes ◽  
Cytosolic Calcium ◽  
Resting Membrane Potential ◽  
Beta Adrenoceptor ◽  
Adrenoceptor Agonist ◽  
Voltage Dependent ◽  
K Concentration ◽  
Ca2 Channels

The effect of the beta-adrenoceptor agonist, isoproterenol, on cytosolic calcium concentration ([Ca2+]i) was studied with the Ca2+-sensitive fluorescent indicator quin 2 in enzymatically dissociated rat ventricular myocytes. Under conditions in which cells have normal polarized resting membrane potential, isoproterenol (1 microM) produced a decrease in [Ca2+]i. In contrast, in the depolarized cells (by raising extracellular K+ concentration to 50 mM), isoproterenol (1 microM) caused an increase in [Ca2+]i. This isoproterenol-induced increase in [Ca2+]i in depolarized cells could be reversed by prior exposure of the cells to the Ca2+ channel blocker, verapamil (5 microM). The results indicate that isoproterenol can either decrease or increase [Ca2+]i depending on membrane potential. The actual effect of isoproterenol on [Ca2+]i at any given membrane potential probably reflects the relative contributions of isoproterenol-induced stimulation of Ca2+ buffering or effluxing activities (which favor a decrease in [Ca2+]i) and enhancement of Ca2+ influx through voltage-sensitive Ca2+ channels (which favors an increase in [Ca2+]i).

Effect of isosmotic removal of extracellular Na+ on cell volume and membrane potential in muscle cells

1994 ◽  
Vol 267 (3) ◽  
pp. C759-C767 ◽  
Author(s):  
C. Pena-Rasgado ◽  
J. C. Summers ◽  
K. D. McGruder ◽  
J. DeSantiago ◽  
H. Rasgado-Flores
Keyword(s):  
Membrane Potential ◽  
Membrane Permeability ◽  
Cell Volume ◽  
Muscle Cells ◽  
Membrane Depolarization ◽  
Cation Channels ◽  
Volume Loss ◽  
Barnacle Muscle ◽  
Nonselective Cation Channels

Isosmotic removal of extracellular Na+ (Nao) is a frequently performed manipulation. With the use of isolated voltage-clamped barnacle muscle cells, the effect of this manipulation on isosmotic cell volume was studied. Replacement of Nao by tris(hydroxymethyl)aminomethane produced membrane depolarization (approximately 20 mV) and cell volume loss (approximately 14%). The membrane depolarization was verapamil insensitive but depended on extracellular Ca2+ (Cao) and was probably due to activation of intracellular Ca2+ (Cai)-dependent nonselective cation channels. The cell volume loss did not require membrane depolarization but depended on Cao. This was probably due to an increase in Cai, mediated by activation of Ca2+ influx via Na+/Ca2+ exchange. Nao replacement by Li+ also promoted membrane depolarization (approximately 20 mV) and cell volume loss (20%). Both effects were reduced (approximately 73%) but were not abolished by Cao removal. Under this condition, the remaining membrane depolarization was probably due to a higher membrane permeability of Li+ over Na+. The remaining cell volume loss was due to membrane depolarization, which probably induced Ca2+ release from intracellular stores.

scholarly journals Non-genomic effects of aldosterone on intracellular ion regulation and cell volume in rat ventricular myocytes

2007 ◽  
Vol 85 (2) ◽  
pp. 264-273 ◽  
Author(s):  
Saori Matsui ◽  
Hiroshi Satoh ◽  
Hirotaka Kawashima ◽  
Shiro Nagasaka ◽  
Chen  Fung Niu ◽  
...  
Keyword(s):  
Cell Volume ◽  
Myocardial Contractility ◽  
Ventricular Myocytes ◽  
Left Ventricular ◽  
Cell Swelling ◽  
Ion Regulation ◽  
Rat Ventricular Myocytes ◽  
Genomic Effects ◽  
Developed Pressure ◽  
Perfused Hearts

Aldosterone has non-genomic effects that express within minutes and modulate intracellular ion milieu and cellular function. However, it is still undefined whether aldosterone actually alters intracellular ion concentrations or cellular contractility. To clarify the non-genomic effects of aldosterone, we measured [Na+]i, Ca2+ transient (CaT), and cell volume in dye-loaded rat ventricular myocytes, and we also evaluated myocardial contractility. We found the following: (i) aldosterone increased [Na+]i at the concentrations of 100 nmol/L to 10 μmol/L; (ii) aldosterone (up to 10 μmol/L) did not alter CaT and cell shortening in isolated myocytes, developed tension in papillary muscles, or left ventricular developed pressure in Langendorff-perfused hearts; (iii) aldosterone (100 nmol/L) increased the cell volume from 47.5 ± 3.6 pL to 49.8 ± 3.7 pL (n = 8, p < 0.05); (iv) both the increases in [Na+]i and cell volume were blocked by a Na+–K+–2Cl– co-transporter (NKCCl) inhibitor, bumetanide, or by a Na+/H+ exchange (NHE) inhibitor, 5-(N-ethyl-N-isopropyl) amiloride; and (v) spironolactone by itself increased in [Na+]i and cell volume. In conclusion, aldosterone rapidly increased [Na+]i and cell volume via NKCC1 and NHE, whereas there were no changes in CaT or myocardial contractility. Hence the non-genomic effects of aldosterone may be related to cell swelling rather than the increase in contractility.

Contribution of a swelling-activated chloride current to changes in the cardiac action potential

1997 ◽  
Vol 273 (2) ◽  
pp. C541-C547 ◽  
Author(s):  
J. I. Vandenberg ◽  
G. C. Bett ◽  
T. Powell
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Action Potentials ◽  
Ventricular Myocytes ◽  
Cell Swelling ◽  
Disulfonic Acid ◽  
Resting Membrane Potential ◽  
Cardiac Action ◽  
Cell Recording ◽  
Induced Changes

The purpose of this investigation was to determine to what extent the swelling-activated Cl- current (ICl,swell) contributes to swelling-induced changes in the resting membrane potential and action potential duration (APD) in ventricular myocytes. Action potentials were recorded from guinea pig ventricular myocytes using conventional whole cell recording techniques. Cell swelling caused initial lengthening followed by a variable shortening of APD. In 59% of cells this secondary APD shortening had a 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)-sensitive component, consistent with a contribution from ICl,swell. Furthermore, DIDS partially antagonized the depolarization of the resting membrane potential that occurred during cell swelling. We have modeled the ICl,swell using the Oxsoft Heart computer program. Action potential changes predicted by the model agree well with the observed DIDS-sensitive component of the change in the action potential during cell swelling. We conclude that activation of ICl,swell contributes to shortening of APD and depolarization of the resting membrane potential during cell swelling in cardiac myocytes.

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