Interrelation of Yin and Yang in Action Potential of Cell Membrane

1998 ◽  
Vol 275 (4) ◽  
pp. H1216-H1224 ◽  
Author(s):  
Seth J. Rials ◽  
Xiaoping Xu ◽  
Ying Wu ◽  
Roger A. Marinchak ◽  
Peter R. Kowey

Recent studies indicate that regression of left ventricular hypertrophy (LVH) normalizes the in situ electrophysiological abnormalities of the left ventricle. This study was designed to determine whether regression of LVH also normalizes the abnormalities of individual membrane currents. LVH was induced in rabbits by renal artery banding. Single ventricular myocytes from rabbits with LVH at 3 mo after renal artery banding demonstrated increased cell membrane capacitance, prolonged action potential duration, decreased inward rectifier K+ current density, and increased transient outward K+ current density compared with myocytes from age-matched controls. Additional rabbits were randomized at 3 mo after banding to treatment with either vehicle or captopril for an additional 3 mo. Myocytes from LVH rabbits treated with vehicle showed persistent membrane current abnormalities. However, myocytes isolated from LVH rabbits treated with captopril had normal cell membrane capacitance, action potential duration, and membrane current densities. Captopril had no direct effect on membrane currents of either control or LVH myocytes. These data support the hypothesis that the action potential prolongation and membrane current abnormalities of LVH are reversed by regression. Normalization of membrane currents probably explains the reduced vulnerability to ventricular arrhythmia observed in this LVH model after treatment with captopril.


1977 ◽  
Vol 197 (1128) ◽  
pp. 333-362 ◽  

A study was made of the time course of the effects of adrenaline and isoprenaline on both twitch tension and the intracellular action potential of single atrial trabeculae from frog heart, under a variety of experimental conditions. Twitch tension and overshoot of action potentials rose and subsided in a parallel fashion during build-up and decline of catecholamine action. Cessation of stimulation during drug application had little effect on the tension responses to the drugs. These, and also results obtained with step changes of external calcium concentration during drug exposure, suggest that tension enhancement is a direct consequence of the increased calcium inward current produced by the catecholamines. Exceptional results from trabeculae of ‘hypodynamic’ hearts are described and interpreted on the basis of previous findings obtained in the ‘hypo-dynamic’ condition. Under suitable conditions, including the use of brief periods of drug exposure (≤20 s), three phases of ( β -catecholamine action were discernible: (1) a latency period, of up to 15 s, which preceded tension and potential rise after drug application. Results are presented suggesting that this latency mainly reflects the time which it takes for drug-combined receptors to activate adenylate cyclase in the cell membrane. (2) A sub­sequent phase was critically dependent, in both its magnitude and time course, on phosphodiesterase activity, as was shown by the application of the specific inhibitors papaverine, ICI 63 197, and Ro 20-1724. This phase is probably controlled by the build-up and decline of cAMP within the cells and the subsequent activation and deactivation of a protein kinase. (3) A third phase, associated with the final portion of the decline of catecholamine action, was relatively insensitive to moderate inhi­bition of phosphodiesterase activity. It is attributed to a change of phosphorylation of sites at the internal surface of the cell membrane, the process which, it is assumed, determines the size of calcium inward current during an action potential. Tension decline after a short staircase occurred with a time course closely similar to that of the final phase of the declining catecholamine response. A common final step in the sequential cellular processes under­ lying the two responses is proposed. In some 40% of the trabeculae examined, adrenaline responses were of ‘mixed’ origin: in addition to the relatively slow β -adrenergic action, an initial rapid tension change was present, and experimental tests suggest that this is mediated by α -type receptors.


1962 ◽  
Vol 203 (2) ◽  
pp. 253-257 ◽  
Author(s):  
Victor Lorber ◽  
John L. Walker ◽  
Ernest A. Greene ◽  
Margaret H. Minarik ◽  
Moon Jae Pak

A phasic effiux of K42 during the cardiac cycle, first described by Wilde in the turtle heart, has been observed in perfused strips of frog ventricle. This was shown to represent an actual increase in the outward movement of K, occurring during the action potential, and of approximately the same duration as the electrical transient. Perfusion with K-free Ringer's prolonged both events, and, within the limits of resolution of the method, appeared to do so to about the same extent. The level of K in the perfusion medium was found to have a pronounced effect on the K efflux, a result which may be interpreted in terms of an effect of extracellular [K+] on the permeability of the cell membrane to K. The finding that the increase in K efflux observed during the action potential is much smaller than that predicted from the increase in the voltage gradient (assuming the voltage gradient to be the only variable) is consistent with a diminished K conductance during the action potential.


1962 ◽  
Vol 15 (1) ◽  
pp. 69 ◽  
Author(s):  
GP Findlay

Experiments are described in which a "voltage� clamping" technique has been applied to large ecorticate internodal cells of the freshwater alga Nitella. In this technique, a feedback circuit is used to change the potential difference between the vacuole of the cell and the external medium to some predetermined level and maintain it as close as possible to this level during the electrical activity of the cell. It is shown that the main factor in the phenomena of potential change and current flow, during the initial stages of the action potential in Nitella, is a tran-sient increase in the permeability of the cell membrane to calcium ions, and a consequent flow of these ions into the cell from the external medium.


1986 ◽  
Vol 56 (1) ◽  
pp. 32-49 ◽  
Author(s):  
R. Shingai ◽  
B. N. Christensen

External horizontal cells were enzymatically dissociated from intact catfish (Ictalurus punctatus) retina and pipetted onto a small chamber attached to the stage of an inverted phase-contrast microscope. Individual horizontal cells were recognized by their large size and restricted dendritic arborization. Low-resistance (3-12 M omega) patch-type electrodes were used to record intracellular potentials and to pass current across the cell membrane under either current or voltage-clamp conditions. The average resting potential of isolated horizontal cells was -67 V + 6.9 mV (mean +/- SD, n = 40). At the resting potential, the cell membrane appears to be mainly permeable to K. A depolarizing current step evoked an action potential in the cell. The maximum rate of rise of the action potential (dV/dt) in normal physiological solution was 6.5 +/- 1.8 V/s (means +/- SD, n = 24) and was reduced to 1.2 +/- 0.39 V/s (means +/- SD, n = 9) in 1-10 micron tetrodotoxin (TTX) and 3.2 +/- 1.4 V/s (means +/- SD, n = 6) in Ca-free solution. The maximum dV/dt was reduced in 10 mM extracellular K concentration [K]o to about half of that seen in standard saline, and values in 30 or 80 mM [K]o were similar to that measured in TTX. Following an action potential, the membrane potential reached a plateau potential of + 17.4 +/- 8.1 mV (means +/- SD, n = 17) and remained depolarized for variable periods of time lasting from less than a second to a few minutes. When the plateau potential was long lasting, the cell repolarized slowly and upon reaching zero rapidly repolarized to the original resting potential. The duration of the plateau potential decreased or was absent in saline containing one of the following calcium channel antagonists: La, Cd, Co, or Ni. The voltage-clamp technique was used to identify the membrane currents responsible for the membrane potential changes seen under current clamp. Experiments were carried out using either a single or two individual electrodes. Fast and steady-state inward currents were recorded from isolated horizontal cells in the voltage range between -20 and +20 mV. These currents were a result of increased membrane conductance to both Na and Ca ions. The Na channels are inactivated at depolarized potentials and are TTX sensitive. Ca channels are partially inactivated at depolarized potentials. The Ca conductance is decreased by Cd, Co, Ni, and La. Ba can substitute for Ca in the channel.(ABSTRACT TRUNCATED AT 400 WORDS)


1960 ◽  
Vol 198 (3) ◽  
pp. 547-551 ◽  
Author(s):  
F. Ware ◽  
A. L. Bennett ◽  
A. R. McIntyre

Membrane potentials were recorded in isolated frog hearts. Observations were made on the effects of calcium deficiency upon resting potential, action potential, overshoot, maximum depolarization rate and action potential contour. Calcium deficiency caused a significant fall in all observed potentials. Maximum depolarization rate was increased. Early repolarization rate was markedly decreased. Chelation of calcium caused changes indistinguishable from those caused by omission of the ion from the perfusate. These results are discussed in relation to current concepts.


2019 ◽  
Author(s):  
Sam Coveney ◽  
Richard H. Clayton

AbstractCardiac cell models reconstruct the action potential and calcium dynamics of cardiac myocytes, and are becoming widely used research tools. These models are highly detailed, with many parameters in the equations that describe current flow through ion channels, pumps, and exchangers in the cell membrane, and so it is difficult to link changes in model inputs to model behaviours. The aim of the present study was to undertake sensitivity and uncertainty analysis of two models of the human atrial action potential. We used Gaussian processes to emulate the way that 11 features of the action potential and calcium transient produced by each model depended on a set of. The emulators were trained by maximising likelihood conditional on a set of design data, obtained from 300 model evaluations. For each model evaluation, the set of inputs was obtained from uniform distributions centred on the default values for each parameter, using latin-hypercube sampling. First order and total effect sensitivity indices were calculated for each combination of input and output. First order indices were well correlated with the square root of sensitivity indices obtained by partial least squares regression of the design data. The sensitivity indices highlighted a difference in the balance of inward and outward currents during the plateau phase of the action potential in each model, with the consequence that changes to one parameter can have opposite effects in the two models. Overall the interactions among inputs were not as important as the first order effects, indicating that model parameters tend to have independent effects on the model outputs. This study has shown that Gaussian process emulators are an effective tool for sensitivity and uncertainty analysis of cardiac cell models.Author summaryThe time course of the cardiac action potential is determined by the balance of inward and outward currents across the cell membrane, and these in turn depend on dynamic behaviour of ion channels, pumps and exchangers in the cell membrane. Cardiac cell models reconstruct the action potential by representing transmembrane current as a set of stiff and nonlinear ordinary differential equations. These models capture biophysical detail, but are complex and have large numbers of parameters, so cause and effect relationships are difficult to identify. In recent years there has been an increasing interest in uncertainty and variability in computational models, and a number of tools have been developed. In this study we have used one of these tools, Gaussian process emulators, to compare and contrast two models of the human atrial action potential. We obtained sensitivity indices based on the proportion of variance in a model output that is accounted for by variance in each of the model parameters. These sensitivity indices highlighted the model parameters that had the most influence on the model outputs, and provided a means to make a quantitative comparison between the models.


2002 ◽  
Vol 282 (1) ◽  
pp. H72-H79 ◽  
Author(s):  
Vinod Sharma ◽  
Leslie Tung

Although intracellular calcium ([Ca2+]i) transients in cardiac cells have been well studied in the uniformly polarized cell membrane, how these transients are modified during field stimulation when the cell membrane is nonuniformly polarized has not been investigated. In this study we characterized the effects of uniform field stimuli on [Ca2+]i transients in isolated guinea pig cardiac cells. Single guinea pig cells were enzymatically isolated, loaded with the [Ca2+]i fluorescent indicator fluo-3, and stimulated along their longitudinal axes with S1 or S1-S2 (S1-S2 = 50 ms) pulses. The fluorescence signals were recorded simultaneously from up to 12 sites along the cell length using a multisite mapping system. S1 pulse, applied during the resting phase of the action potential, induced [Ca2+]itransients that had an earlier onset at the anodal-facing end, suggesting that [Ca2+]i gradients (∇[Ca2+]i) develop during the rising phase of the [Ca2+]i transients. With the assumption that the peak change in [Ca2+]i is 980 nM, ∇[Ca2+]i was estimated to be ∼3.4 nM/μm in the anodal half of the cell for a nominal 10 V/cm field and negligible in the cathodal half. The S2 pulse that was applied during the plateau of the action potential also perturbed the [Ca2+]i transients and produced [Ca2+]i gradients directed from the center to either end of the cell. Mean ∇[Ca2+]i in the anodal half of the cell (∼4.2 nM/μm) was found to be statistically higher than in the cathodal half (∼2.8 nM/μm).


1961 ◽  
Vol 44 (3) ◽  
pp. 443-467 ◽  
Author(s):  
Edward A. Johnson ◽  
J. Tille

Current has been passed through the cell membrane of muscle fibres of the isolated rabbit right ventricle with the aid of intracellular double-barrelled microelectrodes. Two types of muscle fibres were distinguished which are called P and V fibres. The relation between the intensity of a hyperpolarising current applied during the rising phase and the maximum amplitude of the action potential was different in these fibres. For P fibres the relation was essentially linear over most of the range of currents used. For V fibres the change in maximum action potential amplitude was either negligible or did not appear until a certain value of hyperpolarising current was reached. This behaviour of V fibres can be understood if a drop in polarisation resistance occurs during the rising phase and is of such short duration that the polarisation resistance has returned to its resting value before the crest of the action potential is reached. P fibres have an estimated mean resting polarisation resistance of (106 ± 13) K ohms, and a rheobase current strength of (0.08 ± 0.02) µa. In V fibres the resting polarisation resistance was (47 ± 29) K ohms and the rheobase current strength (0.47 ± 0.28) µa.


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