Mechanism of the Effect of Acetate on Frog Ventricular Muscle

1974 ◽  
Vol 52 (3) ◽  
pp. 404-423 ◽  
Author(s):  
Esther R. Anderson ◽  
J. G. Foulks

Substitution of acetate for external Cl produced a large persistent increase in the resting membrane potential (R.M.P.) of frog ventricle and a somewhat steeper relation between membrane potential (M.P.) and [K]o (external K concentration). An increased K conductance or reduced permeability to other ions could account for most of these results, but not for hyperpolarizations as great as −110 mV. Potentials of this size suggested a contribution from an active electrogenic transport system, but they were unaffected by several treatments including exposure to ouabain (10−7 M − 5 × 10−6 M), dinitrophenol (10−6 M, 10−5 M) or 30 mM tetraethylammonium.Acetate caused a prolongation of the action potential (A.P.) and a change in its configuration. Acetate also enhanced twitch tension and increased the rate of tension development. Similar changes are produced by removal of [K]o. The effects of both acetate and K removal on A.P. configuration were prevented by a reduced rate of stimulation.When acetate-induced hyperpolarization was reversed by raising [K]o to 10–15 mM, the configuration of the A.P. resembled that of controls and twitch tension did not increase. Thus, acetate-induced changes in the shape of the A.P. and in twitch tension appeared to be secondary to the increase in R.M.P. However, the relationship does not seem to be direct because these changes were temporary, whereas hyperpolarization was persistent.The character of the acetate-induced changes in A.P. configuration, and the dependence on stimulation rate and [Ca]o (external Ca concentration), suggested a raised [Ca]i (internal Ca concentration) and a possible increase in Ca influx. However, addition of Mn to the acetate solution did not prevent initial acetate-induced changes in the shape of the A.P. plateau and in twitch tension. Also in the absence of [Ca]o, disappearance of twitch tension was slowed by acetate. But acetate decreased the contracture tension produced in response to either increased [K]o or Na removal. Acetate may cause a redistribution of Ca within the cell.

1987 ◽  
Vol 65 (9) ◽  
pp. 1821-1831 ◽  
Author(s):  
E. Honoré ◽  
M. M. Adamantidis ◽  
B. A. Dupuis ◽  
C. E. Challice ◽  
P. Guilbault

Biphasic contractions have been obtained in guinea-pig papillary muscle by inducing partial depolarization in K+-rich solution (17 mM) containing 0.3 μM isoproterenol; whereas in guinea-pig atria, the same conditions led to monophasic contractions corresponding to the first component of contraction in papillary muscle. The relationships between the amplitude of the two components of the biphasic contraction and the resting membrane potential were sigmoidal curves. The first component of contraction was inactivated for membrane potentials less positive than those for the second component. In Na+-low solution (25 mM), biphasic contraction became monophasic subsequent to the loss of the second component, but tetraethylammonium unmasked the second component of contraction. The relationship between the amplitude of the first component of contraction and the logarithm of extracellular Ca2+ concentration was complex, whereas for the second component it was linear. When Ca2+ ions were replaced by Sr2+ ions, only the second component of contraction was observed. It is suggested that the first component of contraction may be triggered by a Ca2+ release from sarcoplasmic reticulum, induced by the fast inward Ca2+ current and (or) by the depolarization. The second component of contraction may be due to a direct activation of contractile proteins by Ca2+ entering the cell along with the slow inward Ca2+ current and diffusing through the sarcoplasm. These results do not exclude the existence of a third "tonic" component, which could possibly be mixed with the second component of contraction.


1999 ◽  
Vol 277 (5) ◽  
pp. H2050-H2064 ◽  
Author(s):  
Frank Brasch ◽  
Marion Neckel ◽  
Rolf Volkmann ◽  
Gerhard Schmidt ◽  
Gerhard Hellige ◽  
...  

The influence on myocyte viability of ischemia-induced changes in capillary perfusion was studied in the hearts of anesthetized rats subjected to partial occlusion of the left coronary artery for 45 min. Timed plasma labeling was applied to determine perfusion patterns. Changes in the fluorescence of preloaded potential-sensitive dyes [tetramethylrhodamine methyl ester (TMRM) and bis-oxonol], of trypan blue, and of endogeneous NADH were utilized in characterizing myocyte viability in histological sections of the heart. Within the hypoperfused zone, localized areas appeared vascularly nonlabeled for periods of at least 10 min. Within these areas a reduction in TMRM fluorescence occurred in 82.5% of the tissue, signaling a reduced resting membrane potential. In the same areas 37.7% of the myocytes revealed an NADH fluorescence lower than that regularly found in anoxic tissues. This correlated with an especially low level of TMRM, with increased fluorescence bis-oxonol and with an accumulation of trypan blue. In conclusion, in localized hypoperfusion-induced zones lacking capillary flow, an inhomogeneous pattern of reductions in myocyte viability develops, which appears to be relevant in ischemia-induced arrhythmias.


1995 ◽  
Vol 18 (11) ◽  
pp. 731-734
Author(s):  
B. Redaelli ◽  
D. Limido ◽  
P. Beretta ◽  
M.R. Viganò

The aim of this study is to evaluate the relationship between two different procedures for potassium removal during hemodialysis (HD) and cardiac arrhythmias. Cell excitability and the transmission of impulses may be influenced by variations of resting membrane potential (RMP). The rapid decrease of plasma potassium during the first two hours of standard HD causes a membrane hyperpolarization. A different K+ kinetic, with a gradual and constant elimination of K+ during HD, may reduce this further unphysiological aspect and its clinical consequences. This can be obtained keeping blood-dialysate K+ gradient as constant as possible with the use of a dialysate K+ concentration (Kd) decreasing during HD. Our experimental studies on various K+ intradialytic gradients seem to indicate as optimal to this purpose K+ gradients of 1.5 mEq/l at the beginning of dialysis, esponentially decreasing during treatment to Kd values of 2.5 mEq/l at the end of dialysis (variable Kd). Patients included in the trial will be submitted to two different methods of treatment with Kd 2 mEq/l and variable Kd, and to a 24 hours ECG the day of dialysis. We will compare the number of intra and interdialytic premature ventricular complexes to evaluate the impact of two different models of potassium removal on arrhythmias.


1987 ◽  
Vol 252 (4) ◽  
pp. H697-H703 ◽  
Author(s):  
S. S. Sheu ◽  
V. K. Sharma ◽  
M. Korth

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).


1996 ◽  
Vol 314 (1) ◽  
pp. 339-345 ◽  
Author(s):  
Jesper GROMADA ◽  
Jørgen FRØKJÆR-JENSEN ◽  
Steen DISSING

The cellular processes leading to a rise in the intracellular free Ca2+ concentration ([Ca2+]i) after glucose stimulation and K+ depolarization were investigated in insulin-secreting βTC3 cells. Stimulation with 11.2 mM glucose causes inositol 1,4,5-trisphosphate production and release of Ca2+ from intracellular stores. A strong correlation was observed between the changes in Ins(1,4,5)P3 concentration and the rise in [Ca2+]i, consistent with the former compound being responsible for release of Ca2+ from intracellular stores. The increase in Ins(1,4,5)P3 production was reduced by 68±4% when [Ca2+]i was kept low on glucose stimulation by loading cells with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-NNN´N´-tetra-acetic acid (BAPTA). The Ins(1,4,5)P3 production was prevented in cells hyperpolarized with diazoxide, an opener of ATP-sensitive K+-channels, consistent with the membrane potential controlling the rate of Ins(1,4,5)P3 synthesis. Depolarizing K+ concentrations evoked changes in [Ca2+]i and Ins(1,4,5)P3 production in both the presence and the absence of extracellular Ca2+, and from the relation between the extracellular K+ concentration and membrane potential we found a half-maximal Ins(1,4,5)P3 production by a 28 mV depolarization from a resting potential of -56 mV and by a rise in [Ca2+]i of 390 nM. We conclude that stimulation-induced changes in membrane potential and [Ca2+]i are important in controlling Ins(1,4,5)P3 production in βTC-3 cells and that glucose-stimulated Ca2+ mobilization from intracellular stores is due to voltage-dependent Ins(1,4,5)P3 production and depends on the concurrent increase in [Ca2+]i.


1996 ◽  
Vol 199 (6) ◽  
pp. 1335-1341
Author(s):  
W Wuttke ◽  
T Munsch ◽  
J Deitmer

The effects of extracellular ATP on intracellular free Ca2+ concentration ([Ca2+]i) and depolarization-induced elevations of [Ca2+]i were investigated in salivary cells of the leech Haementeria ghilianii using the fluorescent Ca2+ indicator Fura-2. Simultaneously, the membrane potential was monitored or controlled by voltage-clamp. The cell membrane was depolarized either by transient elevations of the extracellular K+ concentration ([K+]o) to 90 mmol l-1 or by depolarizing steps under voltage-clamp. The resulting transient elevations of [Ca2+]i (Ca2+ transients) could be repeatedly elicited with little variability in amplitude. Ca2+ transients were completely inhibited by 2 mmol l-1 Ni2+ or in Ca2+-free saline. The transients are, therefore, dependent on Ca2+ influx from the external medium through voltage-gated Ca2+ channels. The Ca2+ influx was rapidly and reversibly inhibited by extracellular application of ATP. The effect was dose-dependent with a threshold concentration below 10(-7) mol l-1. A 50 % reduction in the amplitude of Ca2+ transients was obtained by application of 1­2 µmol l-1 ATP or ATP-gamma-S (apparent IC50, 1.6 µmol l-1 ATP) and Ca2+ transients were almost completely inhibited by 30­100 µmol l-1 ATP. Resting [Ca2+]i, the resting membrane potential and membrane potential changes induced by 90 mmol l-1 [K+]o were not affected by ATP. Adenosine (10 µmol l-1) did not affect resting [Ca2+]i, the resting membrane potential or membrane potential changes induced by 90 mmol l-1 [K+]o and had little effect on Ca2+ transients. Suramin, an antagonist of vertebrate P2 receptors, was without effect on the inhibitory actions of ATP. We conclude that activation of a suramin-insensitive purinoceptor by ATP inhibits Ca2+ influx through voltage-gated Ca2+ channels in the salivary cells of Haementeria ghilianii.


1978 ◽  
Vol 71 (5) ◽  
pp. 467-488 ◽  
Author(s):  
C Caputo ◽  
R Dipolo

Tension development in voltage-clamped barnacle muscle fibers occurs with depolarizing pulses so small as not to activate the potassium and calcium conductance systems. Peak tension and the tension time integral appear to be graded by both amplitude and duration of the depolarizing pulses. Subthreshold depolarizing conditioning pulses shorter than 500 ms potentiate the response to a given test pulse. This effect diminishes and reverts when the duration of the conditioning pulse is increasingly prolonged. The relationship between fiber membrane potential and tension developed in response to depolarizing pulses is described by an S-shaped curve. The tension saturates at a membrane potential of about +10 mV (inside positive). For a given pulse duration the saturation value remains constant even when the fiber interior reaches a value of +230 mV, which is well above what may be estimated to be the equilibrium potential of calcium ions (Eca = +120). In the presence of 5 mM external procaine, the shape of the tension-potential curve changes; the maximum value tension besides being diminished is not sustained by falls when the potential approaches the estimated value for Eca. These results suggest that under physiological conditions the contractile activator is probably released from an internal store, and that the calcium entering the fiber as inward current does not play a direct major role in contractile activation.


1973 ◽  
Vol 51 (10) ◽  
pp. 709-726 ◽  
Author(s):  
Esther R. Anderson ◽  
J. G. Foulks

The effects of replacement of external chloride by other anions on the electrical and mechanical properties of frog ventricular muscle have been studied.The effects of methylsulfate were similar to those expected for replacement of a permeant anion with an impermeant anion. Increased twitch tension was largely dependent on action potential prolongation. Other anions of the sulfate–sulfonate series produced similar changes, but minor differences in their actions indicated that their effects could not be explained entirely by the elimination of chloride current.Acetate and its analogues produced dramatic changes in both the electrical and mechanical properties of frog heart. All caused a marked hyperpolarization of the resting membrane potential, accompanied by characteristic changes in the shape and duration of the repolarization phase of the action potential. Enhanced contractile performance was characterized by an increased rate of tension development and a slow onset of relaxation. These effects were equally prominent upon transfer to acetate Ringer's solution after previous equilibration to a medium containing methylsulfate in place of chloride. Although similar qualitatively, the members of this series of anions also displayed marked quantitative differences in the intensity and time course of their effects.


1987 ◽  
Vol 89 (3) ◽  
pp. 443-457 ◽  
Author(s):  
M Kashiwayanagi ◽  
K Sai ◽  
K Kurihara

A suspension of olfactory epithelial cells was prepared from porcine olfactory mucosa and the physiological functions of the suspension were examined. The membrane potential of the cell suspension, which was monitored by measuring the fluorescence changes of rhodamine 6G, was depolarized by an increase in the K+ concentration in the external medium. Various odorants depolarized the cell suspension in a dose-dependent fashion. The magnitude of depolarization by odorants was either unchanged or slightly increased by a reduction of the concentration of Na+, Ca2+, and Cl- in the external medium, which suggests that changes in the permeabilities of specific ions are not involved in depolarization by odorants. The application of various odorants to the cell suspension induced changes in the membrane fluidity at different sites of the membrane that were monitored with various fluorescent dyes [8-anilino-1-naphthalene sulfonate, n-(9-anthroyloxy) stearic acids, 12-(9-anthroyloxy) oleic acid, and (1,6-diphenyl-1,3,5-hexatriene)], which suggests that the odorants having different odors are adsorbed on different sites in the membrane. On the basis of these results, a possible mechanism of odor discrimination is discussed.


1997 ◽  
Vol 273 (2) ◽  
pp. C541-C547 ◽  
Author(s):  
J. I. Vandenberg ◽  
G. C. Bett ◽  
T. Powell

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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