Modulation of membrane potential by an acetylcholine-activated potassium current in trout atrial myocytes

2007 ◽  
Vol 292 (1) ◽  
pp. R388-R395 ◽  
Author(s):  
Cristina E. Molina ◽  
Hans Gesser ◽  
Anna Llach ◽  
Lluis Tort ◽  
Leif Hove-Madsen
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Ventricular Myocytes ◽  
Reversal Potential ◽  
Membrane Potentials ◽  
Resting Membrane Potential ◽  
Atrial Myocytes ◽  
Atrial Tissue ◽  
Isolated Cardiac Myocytes ◽  
Inwardly Rectifying

Application of the current-clamp technique in rainbow trout atrial myocytes has yielded resting membrane potentials that are incompatible with normal atrial function. To investigate this paradox, we recorded the whole membrane current ( Im) and compared membrane potentials recorded in isolated cardiac myocytes and multicellular preparations. Atrial tissue and ventricular myocytes had stable resting potentials of −87 ± 2 mV and −83.9 ± 0.4 mV, respectively. In contrast, 50 out of 59 atrial myocytes had unstable depolarized membrane potentials that were sensitive to the holding current. We hypothesized that this is at least partly due to a small slope conductance of Im around the resting membrane potential in atrial myocytes. In accordance with this hypothesis, the slope conductance of Im was about sevenfold smaller in atrial than in ventricular myocytes. Interestingly, ACh increased Im at −120 mV from 4.3 pA/pF to 27 pA/pF with an EC50 of 45 nM in atrial myocytes. Moreover, 3 nM ACh increased the slope conductance of Im fourfold, shifted its reversal potential from −78 ± 3 to −84 ± 3 mV, and stabilized the resting membrane potential at −92 ± 4 mV. ACh also shortened the action potential in both atrial myocytes and tissue, and this effect was antagonized by atropine. When applied alone, atropine prolonged the action potential in atrial tissue but had no effect on membrane potential, action potential, or Im in isolated atrial myocytes. This suggests that ACh-mediated activation of an inwardly rectifying K+ current can modulate the membrane potential in the trout atrial myocytes and stabilize the resting membrane potential.

Electrophysiological response of rat ventricular myocytes to acidosis

2002 ◽  
Vol 283 (1) ◽  
pp. H412-H422 ◽  
Author(s):  
Kimiaki Komukai ◽  
Fabien Brette ◽  
Caroline Pascarel ◽  
Clive H. Orchard
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Ventricular Myocytes ◽  
Resting Potential ◽  
Disulfonic Acid ◽  
Resting Membrane Potential ◽  
Delayed Rectifier ◽  
Patch Clamp Technique ◽  
Electrophysiological Response ◽  
Inwardly Rectifying

The effects of acidosis on the action potential, resting potential, L-type Ca2+( I Ca), inward rectifier potassium ( I K1), delayed rectifier potassium ( I K), steady-state ( I SS), and inwardly rectifying chloride ( I Cl,ir) currents of rat subepicardial (Epi) and subendocardial (Endo) ventricular myocytes were investigated using the patch-clamp technique. Action potential duration was shorter in Epi than in Endo cells. Acidosis (extracellular pH decreased from 7.4 to 6.5) depolarized the resting membrane potential and prolonged the time for 50% repolarization of the action potential in Epi and Endo cells, although the prolongation was larger in Endo cells. At control pH, I Ca, I K1, and I SS were not significantly different in Epi and Endo cells, but I K was larger in Epi cells. Acidosis did not alter I Ca, I K1, or I K but decreased I SS; this decrease was larger in Endo cells. It is suggested that the acidosis-induced decrease in I SS underlies the prolongation of the action potential. I Cl,ir at control pH was Cd2+ sensitive but 4,4′-disothiocyanato-stilbene-2,2′-disulfonic acid resistant. Acidosis increased I Cl,ir; it is suggested that the acidosis-induced increase in I Cl,ir underlies the depolarization of the resting membrane potential.

scholarly journals Chloride current in mammalian cardiac myocytes. Novel mechanism for autonomic regulation of action potential duration and resting membrane potential.

1990 ◽  
Vol 95 (6) ◽  
pp. 1077-1102 ◽  
Author(s):  
R D Harvey ◽  
C D Clark ◽  
J R Hume
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Cardiac Myocytes ◽  
Action Potential Duration ◽  
Ventricular Myocytes ◽  
Reversal Potential ◽  
Chloride Current ◽  
Equilibrium Potential ◽  
Resting Membrane Potential ◽  
Dependent Pathway

The properties of the autonomically regulated chloride current (ICl) were studied in isolated guinea pig ventricular myocytes. This current was elicited upon exposure to isoproterenol (ISO) and reversed upon concurrent exposure to acetylcholine (ACh). ICl was time independent and exhibited outward rectification. The responses to ISO and ACh could be blocked by propranolol and atropine, respectively, and ICl was also elicited by forskolin, 8-bromoadenosine 3',5'-cyclic monophosphate, and 3-isobutyl-l-methylxanthine, indicating that the current is regulated through a cAMP-dependent pathway. The reversal potential of the ISO-induced current followed the predicted chloride equilibrium potential, consistent with it being carried predominantly by Cl-. Activation of ICl produced changes in the resting membrane potential and action potential duration, which were Cl- gradient dependent. These results indicate that under physiological conditions ICl may play an important role in regulating action potential duration and resting membrane potential in mammalian cardiac myocytes.

scholarly journals Electrophysiological response of rat atrial myocytes to acidosis

2002 ◽  
Vol 283 (2) ◽  
pp. H715-H724 ◽  
Author(s):  
Kimiaki Komukai ◽  
Fabien Brette ◽  
Clive H. Orchard
Keyword(s):  
Steady State ◽  
Membrane Potential ◽  
Action Potential ◽  
Disulfonic Acid ◽  
Resting Membrane Potential ◽  
Bathing Solution ◽  
Atrial Myocytes ◽  
Patch Clamp Technique ◽  
Electrophysiological Response ◽  
Inwardly Rectifying

The effect of acidosis on the electrical activity of isolated rat atrial myocytes was investigated using the patch-clamp technique. Reducing the pH of the bathing solution from 7.4 to 6.5 shortened the action potential. Acidosis had no significant effect on transient outward or inward rectifier currents but increased steady-state outward current. This increase was still present, although reduced, when intracellular Ca2+ was buffered by 1,2-bis(2-aminophenoxy)ethane- N,N,N′,N′-tetraacetic acid (BAPTA); BAPTA also inhibited acidosis-induced shortening of the action potential. Ni2+ (5 mM) had no significant effect on the acidosis-induced shortening of the action potential. Acidosis also increased inward current at −80 mV and depolarized the resting membrane potential. Acidosis activated an inwardly rectifying Cl− current that was blocked by 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS), which also inhibited the acidosis-induced depolarization of the resting membrane potential. It is concluded that an acidosis-induced increase in steady-state outward K+ current underlies the shortening of the action potential and that an acidosis-induced increase in inwardly rectifying Cl− current underlies the depolarization of the resting membrane potential during acidosis.

scholarly journals K+ currents regulate the resting membrane potential, proliferation, and contractile responses in ventricular fibroblasts and myofibroblasts

2005 ◽  
Vol 288 (6) ◽  
pp. H2931-H2939 ◽  
Author(s):  
L. Chilton ◽  
S. Ohya ◽  
D. Freed ◽  
E. George ◽  
V. Drobic ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Reversal Potential ◽  
Mechanical Activity ◽  
Resting Membrane Potential ◽  
Whole Cell Patch Clamp ◽  
Voltage Dependent ◽  
Primary Determinant ◽  
Inwardly Rectifying ◽  
Low K ◽  
Ionic Basis

Despite the important roles played by ventricular fibroblasts and myofibroblasts in the formation and maintenance of the extracellular matrix, neither the ionic basis for membrane potential nor the effect of modulating membrane potential on function has been analyzed in detail. In this study, whole cell patch-clamp experiments were done using ventricular fibroblasts and myofibroblasts. Time- and voltage-dependent outward K+ currents were recorded at depolarized potentials, and an inwardly rectifying K+ (Kir) current was recorded near the resting membrane potential (RMP) and at more hyperpolarized potentials. The apparent reversal potential of Kir currents shifted to more positive potentials as the external K+ concentration ([K+]o) was raised, and this Kir current was blocked by 100–300 μM Ba2+. RT-PCR measurements showed that mRNA for Kir2.1 was expressed. Accordingly, we conclude that Kir current is a primary determinant of RMP in both fibroblasts and myofibroblasts. Changes in [K+]o influenced fibroblast membrane potential as well as proliferation and contractile functions. Recordings made with a voltage-sensitive dye, DiBAC3(4), showed that 1.5 mM [K+]o resulted in a hyperpolarization, whereas 20 mM [K+]o produced a depolarization. Low [K+]o (1.5 mM) enhanced myofibroblast number relative to control (5.4 mM [K+]o). In contrast, 20 mM [K+]o resulted in a significant reduction in myofibroblast number. In separate assays, 20 mM [K+]o significantly enhanced contraction of collagen I gels seeded with myofibroblasts compared with control mechanical activity in 5.4 mM [K+]o. In combination, these results show that ventricular fibroblasts and myofibroblasts express a variety of K+ channel α-subunits and demonstrate that Kir current can modulate RMP and alter essential physiological functions.

scholarly journals Current Separations in Myxicola Giant Axons

1969 ◽  
Vol 54 (6) ◽  
pp. 741-754 ◽  
Author(s):  
L. Goldman ◽  
L. Binstock
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Reversal Potential ◽  
Transient Current ◽  
Resting Potential ◽  
Equilibrium Potential ◽  
Resting Membrane Potential ◽  
Concentration Data ◽  
Giant Axons ◽  
Current Reversal

The effect of reducing the external sodium concentration, [Na]o, on resting potential, action potential, membrane current, and transient current reversal potential in Myxicola giant axons was studied. Tris chloride was used as a substitute for NaCl. Preliminary experiments were carried out to insure that the effect of Tris substitution could be attributed entirely to the reduction in [Na]o. Both choline and tetramethylammonium chloride were found to have additional effects on the membrane. The transient current is carried largely by Na, while the delayed current seems to be independent of [Na]o. Transient current reversal potential behaves much like a pure Nernst equilibrium potential for sodium. Small deviations from this behavior are consistent with the possibility of some small nonsodium component in the transient current. An exact PNa/PK for the transient current channels could not be computed from these data, but is certainly well greater than unity and possibly quite large. The peak of the action potential varied with [Na]o as expected for a sodium action potential with some substantial potassium permeability at the time of peak. Resting membrane potential is independent of [Na]o. This finding is inconsistent with the view that the resting membrane potential is determined only by the distribution of K and Na, and PNa/PK. It is suggested that PNa/PK's obtained from resting membrane potential-potassium concentration data do not always have the physical meaning generally attributed to them.

Rat hippocampal astrocytes exhibit electrogenic sodium-bicarbonate co-transport

1994 ◽  
Vol 72 (6) ◽  
pp. 2580-2589 ◽  
Author(s):  
E. R. O'Connor ◽  
H. Sontheimer ◽  
B. R. Ransom
Keyword(s):  
Membrane Potential ◽  
Reversal Potential ◽  
Input Resistance ◽  
Membrane Potentials ◽  
Resting Membrane Potential ◽  
Induced Response ◽  
Potential Range ◽  
Free Solution ◽  
Hippocampal Astrocytes ◽  
In Cells

1. We probed for the expression of electrogenic Na+/HCO3- co-transport in cultured mammalian astrocytes by recording voltage and current changes induced by bath application of HCO3-, with the use of patch-clamp electrophysiology. Application of 25 mM HCO3-, at a constant pHo, to astrocytes bathed in a nominally HCO3(-)-free solution, produced an abrupt and reversible change in membrane potential ranging from +3 to -30 mV [-11.8 +/- 9.34 (SD) mV]; 55% of cells showed relatively large hyperpolarizing responses (-18.8 +/- 6.23 mV), whereas 45% showed only small shifts in membrane potential (range of -5 to +3 mV; -1.9 +/- 1.96 mV). 2. The size of the HCO3(-)-induced hyperpolarization was strongly related to the cell's initial resting membrane potential in HCO3(-)-free solution; the larger responses were seen in cells with relatively low resting membrane potentials (-48.5 +/- 9.4 mV), and the smaller responses were seen in cells with more negative potentials (-68.1 +/- 6.5 mV). The membrane potentials of hippocampal astrocytes were highly variable in HCO3(-)-free solution (range -38 to -80 mV; -60.9 +/- 12.53); this variability was greatly reduced in HCO3(-)-containing solution (range -59 to -82 mV; -68.5 +/- 4.8). 3. The magnitude of the HCO3(-)-induced response was less strongly correlated with cell input resistance, which was higher in the larger responder cells than in the small responders. However, the differences in input resistance were insufficient to account for the different HCO3(-)-induced responses observed. 4. In the presence of extracellular Ba2+, which by blocking K+ conductance depolarized cells by 30-50 mV, cells that initially showed a small response, showed a large and completely reversible hyperpolarization (-18.4 +/- 6.13 mV) to application of 25 mM HCO3-. In Na(+)-free solution, the HCO3(-)-induced hyperpolarization was reduced by 66%, and the response was not sustained, as in Na(+)-containing solution. Removal of extracellular Cl- had no effect on the HCO3- response The stilbene derivative 4,4'-diisothiocyano-2,2'-stilbene disulfonate (DIDS), a blocker of anion transport, eliminated the HCO3(-)-induced hyperpolarization. Blockers of Na+/K+ ATPase and Na(+)-H+ exchange were without effect. These observations indicated the presence of an electrogenic Na+/HCO3- co-transporter in hippocampal astrocytes. 6. Voltage-clamp recording demonstrated that the HCO3(-)-induced hyperpolarization was caused by outward currents averaging 335 +/- 104 pA. The reversal potential of the HCO3(-)-induced current ranged between -80 and -99 mV with an average = -86.1 +/- 6.2 mV.(ABSTRACT TRUNCATED AT 400 WORDS)

Transmembrane potentials in the rat myometrium during pregnancy

1959 ◽  
Vol 196 (4) ◽  
pp. 901-904 ◽  
Author(s):  
John B. Thiersch ◽  
Jorge F. Landa ◽  
Theodore C. West
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Early Pregnancy ◽  
Membrane Potentials ◽  
Resting Membrane Potential ◽  
Intracellular Recordings ◽  
Spike Discharge ◽  
Transmembrane Potentials ◽  
Microelectrode Technique ◽  
Long Evans

Isolated segments of the uteri of pregnant and nonpregnant Long-Evans rats were studied by the microelectrode technique of intracellular recordings. Both action and resting membrane potentials were recorded in the following states: nonpregnant; 12, 15 and 21 days pregnant; and 24 hours postpartum. The results indicated that the magnitude of the resting membrane potential increased with advancing pregnancy when observed from areas exclusive of the sites of placental attachment. However, resting potentials from placental sites were maximum at 12 and 15 days pregnancy. The frequency of spontaneous spike discharge was greatest in nonpregnant uteri and in early pregnancy declining to a minimum at 24 hours postpartum. Oxytocin increased the frequency of spike discharge and increased the duration of repetitive action potential trains. This effect was greatest in early pregnancy and in the nonpregnant uterus.

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.

Contribution of the Hyperpolarization-Activated Current (I h) to Membrane Potential and GABA Release in Hippocampal Interneurons

2001 ◽  
Vol 86 (1) ◽  
pp. 261-268 ◽  
Author(s):  
Carl R. Lupica ◽  
James A. Bell ◽  
Alexander F. Hoffman ◽  
Patricia L. Watson
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Pyramidal Neurons ◽  
Membrane Potentials ◽  
Resting Membrane Potential ◽  
Inhibitory Input ◽  
Ca1 Pyramidal Neurons ◽  
Spontaneous Action Potential ◽  
Spontaneous Action ◽  
Zd 7288

Intrinsic GABAergic interneurons provide inhibitory input to the principal neurons of the hippocampus. The majority of interneurons located in stratum oriens (s.o.) of the CA1 region express the hyperpolarization-activated cation current known as I h. In an effort to elucidate the role of this current in regulating the baseline excitability of these neurons and its participation in the regulation of the release of GABA onto CA1 pyramidal neurons, we utilized whole cell electrophysiological recordings from both populations of cells. In voltage-clamp experiments, hyperpolarization of the interneuron membrane initiated a large inward current with an estimated activation threshold of 51.6 ± 7.6 mV and a half-maximal voltage of −73.0 ± 7.0 mV. This current was blocked by bath application of the I h inhibitors ZD 7288 (50 μM) or cesium (2 mM). Current-clamp experiments at the interneuron resting membrane potential (−61.3 ± 1.2 mV) revealed a significant hyperpolarization, a decrease in the rate of spontaneous action potential discharge, an increase in the cellular input resistance, and the elimination of rebound afterdepolarizations during blockade of I h with ZD 7288 (50 μM). The hyperpolarizing effect of ZD 7288 was also substantially larger in interneurons clamped near −80 mV using current injection through the pipette. In addition to neurons exhibiting I h, recordings were obtained from a small population of s.o. interneurons that did not exhibit this current. These cells demonstrated resting membrane potentials that were significantly more negative (−73.6 ± 5.5 mV) than those observed in neurons expressing I h, suggesting that this current contributes to more depolarized membrane potentials in these cells. Recordings from postsynaptic pyramidal neurons demonstrated that blockade of I h with ZD 7288 caused a substantial reduction (∼43%) in the frequency of spontaneous action potential-dependent inhibitory postsynaptic currents (IPSCs), without altering their average amplitude. However, miniature action-potential-independent IPSC frequency, amplitude, and decay kinetics were unaltered by ZD 7288. These data suggest that I h is active at the resting membrane potential in s.o. interneurons and as a result contributes to the spontaneous activity of these cells and to the tonic inhibition of CA1 pyramidal neurons in the hippocampus.

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