scholarly journals Restitution slope is principally determined by steady-state action potential duration

2017 ◽  
Vol 113 (7) ◽  
pp. 817-828 ◽  
Author(s):  
Michael J. Shattock ◽  
Kyung Chan Park ◽  
Hsiang-Yu Yang ◽  
Angela W. C. Lee ◽  
Steven Niederer ◽  
...  
Keyword(s):  
Steady State ◽  
Action Potential ◽  
Action Potential Duration ◽  
State Action

Isoproterenol antagonizes drug-induced prolongation of action potential duration in humans

1993 ◽  
Vol 71 (10-11) ◽  
pp. 755-760 ◽  
Author(s):  
David Newman ◽  
Paul Dorian ◽  
Randi Feder-Elituv
Keyword(s):  
Steady State ◽  
Action Potential ◽  
Action Potential Duration ◽  
Refractory Period ◽  
Cycle Length ◽  
Monophasic Action Potential ◽  
Class Iii ◽  
State Action ◽  
Cycle Lengths ◽  
Prolongation Of Action Potential

The effects of an isoproterenol infusion on the duration of the human right ventricular endocardial monophasic action potential at 90% repolarization were recorded in the absence and in the presence of an antiarrhythmic drag regimen containing class III effects in two similar groups of patients. The drugs used were amiodarone (N = 3, 300 ± 50 mg), sotalol plus quinidine (N = 11, 156 ± 13 mg sotalol, 1688 ± 594 mg quinidine), and sotalol alone (N = 3, 300 ± 20 mg). All patients had underlying coronary disease but no evidence of inducible ischemia. In the absence of antiarrhythmic drug, isoproterenol did not significantly change the relationship of action potential duration at 90% repolarization to cycle length; there was a linear decrease in action potential duration by 19.8% between a paced cycle length of 600 and 300 ms. Isoproterenol did not significantly shorten the action potential duration at any cycle length. However, isoproterenol decreased the ventricular effective refractory period at 400 ms drive from 240 ± 5.0 to 225 ± 6.0 ms (p < 0.05) accompanied by no change in the ratio of refractory period to steady-state action potential duration. In the presence of class III drug effects, the action potential duration was increased by an average of 9.2% at all paced cycle lengths longer than 300 ms (p < 0.05). The ventricular refractory period was increased from 240 ± 5 to 269 ± 9.0 ms (p < 0.05 compared with baseline) with a concomitant increase in the ratio of refractory period to action potential duration from 96 ± 2 to 103 ± 2% (p < 0.05 compared with baseline). With infusion of isoproterenol in the presence of a class III containing regimen, the drug-prolonged action potential duration was shortened (p < 0.05) by an average of 8.1% at all cycle lengths longer than 300 ms. These results suggest that isoproterenol simulation of enhanced sympathetic tone can antagonize drug prolongation of action potential duration and that in the absence of drugs, the effects of isoproterenol on the steady-state action potential duration are modest. The clinical utility of class III agents may be augmented by the addition of concomitant β-blockade.Key words: action potential duration, antiarrhythmic drugs, isoproterenol.

Effects of myocardial hypertrophy on transient outward current

1994 ◽  
Vol 266 (5) ◽  
pp. H1738-H1745 ◽  
Author(s):  
Q. Li ◽  
E. C. Keung
Keyword(s):  
Steady State ◽  
Action Potential ◽  
Action Potential Duration ◽  
Time Course ◽  
Myocardial Hypertrophy ◽  
Pressure Overload ◽  
Reversal Potential ◽  
Outward Current ◽  
Transient Outward Current ◽  
The Difference

In the one-clip, two-kidney model of hypertensive rat, a gradual chronic pressure overload is imposed on the heart. Myocardial hypertrophy resulting from such pressure overload is associated with an increased but slower inactivating L-type calcium current and prolongation of action potential duration. Voltage clamp experiments in a variety of excitable tissues indicate that a 4-aminopyridine-sensitive transient outward current (Ito) plays an important role in regulating the action potential duration. Accordingly, we studied Ito in single adult cardiac myocytes enzymatically isolated from hypertrophied left ventricles of the renovascular hypertensive (HBP) rat hearts using the whole cell patch-clamp method. The current densities (normalized to cell capacitative surface area) measured at the early transient peak Ito, at the steady state, and as the difference between the transient peak and the steady state were larger in HBP cells (n = 23) than in control (Ctrl) cells (n = 20) (P < 0.05). There was no difference in the Ito reversal potential between Ctrl (-60.9 +/- 1.9 mV, mean +/- SE; n = 16) and HBP (-63.7 +/- 2.6 mV; n = 19) cells. The observed increase in Ito amplitude was not due to an increase in the number of channels available for activation or in the fraction of channels activated because there were no statistical differences in the membrane potential at which one-half of the Ito channels are activated (V0.5) for the steady-state activation and inactivation curves between Ctrl and HBP cells. The time course of inactivation of Ito was described by a double-exponential function.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging-associated changes in whole cell K+ and L-type Ca2+ currents in rat ventricular myocytes

2000 ◽  
Vol 279 (3) ◽  
pp. H889-H900 ◽  
Author(s):  
Shi J. Liu ◽  
Richard P. Wyeth ◽  
Russell B. Melchert ◽  
Richard H. Kennedy
Keyword(s):  
Steady State ◽  
Young Adult ◽  
Action Potential ◽  
Action Potential Duration ◽  
Ventricular Myocytes ◽  
Inactivation Kinetics ◽  
Whole Cell ◽  
Rat Ventricular Myocytes ◽  
Whole Cell Patch Clamp ◽  
Steady State Inactivation

The effect of aging on cardiac membrane currents remains unclear. This study examined the inward rectifier K+ current ( I K1), the transient outward K+current ( I to), and the L-type Ca2+ channel current ( I Ca,L) in ventricular myocytes isolated from young adult (6 mo) and aged (>27 mo) Fischer 344 rats using whole cell patch-clamp techniques. Along with an increase in the cell size and membrane capacitance, aged myocytes had the same magnitude of peak I K1 with a greater slope conductance but displayed smaller steady-state I K1. Aged myocytes also had a greater I to with an increased rate of activation, but the I to inactivation kinetics, steady-state inactivation, and responsiveness to l-phenylephrine, an α1-adrenergic agonist, were unaltered. The magnitude of peak I Ca,L in aged myocytes was decreased and accompanied by a slower inactivation, but the I Ca,L steady-state inactivation was unaltered. Action potential duration in aged myocytes was prolonged only at 90% of full repolarization (APD90) when compared with the action potential duration of young adult myocytes. Aged myocytes from Long-Evans rats showed similar changes in I toand I Ca,L but an increased I K1. These results demonstrate aging-associated changes in action potential, in morphology, and in I K1, I to, and I Ca,L of rat ventricular myocytes that possibly contribute to the decreased cardiac function of aged hearts.

Effect of norepinephrine on Na(+)-K+ pump and Na+ influx in sheep cardiac Purkinje fibers

1990 ◽  
Vol 258 (4) ◽  
pp. C713-C722 ◽  
Author(s):  
S. W. Chae ◽  
D. Y. Wang ◽  
Q. Y. Gong ◽  
C. O. Lee
Keyword(s):  
Steady State ◽  
Membrane Potential ◽  
Action Potential ◽  
Action Potential Duration ◽  
Relative Magnitude ◽  
Resting Membrane Potential ◽  
Pacemaker Current ◽  
Purkinje Fibers ◽  
Cardiac Purkinje Fibers ◽  
High K

Effects of norepinephrine and Ca+ on Na(+)-K+ pump and pacemaker current were investigated by simultaneous measurement of intracellular Na+ activity (aiNa) and membrane potential in driven (1 Hz) and quiescent sheep cardiac Purkinje fibers. Concurrently, twitch force was measured in driven fibers, in which norepinephrine (NE) produced a decrease in aiNa, a prolongation in action potential duration, and a hyperpolarization in diastolic membrane potential, Vdm. In contrast, in quiescent fibers, NE produced an increase in aiNa and a depolarization in resting membrane potential, Vm. The decrease in aiNa, prolongation in action potential duration, and hyperpolarization in Vdm produced by NE were blocked by 5 x 10(-6) M strophanthidin, presumably through inhibition of the Na(+)-K+ pump. The increase in aiNa and membrane depolarization caused by NE were abolished by high [K+]o or Cs+, presumably through inhibition of the pacemaker current, if. These results indicate that in driven fibers NE stimulates predominantly the Na(+)-K+ pump, producing a decrease in aiNa and that in quiescent fibers it increases predominantly if, producing an increase in aiNa. The effect of NE on driven and quiescent fibers differs because of the voltage dependence of if and perhaps the Na(+)-K+ pump. Consequently, the relative magnitude of the two opposing effects of NE on aiNa appears to be dependent on membrane potential. In quiescent fibers, Cs+ monotonically decreased aiNa to a steady-state value, while Cs+ hyperpolarized membrane potential and then slowly depolarized to a steady-state level, producing a transient hyperpolarization. In driven fibers, Cs+ decreased aiNa, shortened action potential duration, and depolarized Vdm. Cs+ decreased aiNa more in quiescent fibers than in driven fibers. The decrease in aiNa and hyperpolarization in membrane potential produced by Cs+ in quiescent fibers were abolished by depolarization induced by high K+ extracellular concentration (25.4 mM) but were not abolished or reduced by 5 x 10(-6) M strophanthidin. These results suggest that the decrease in aiNa and hyperpolarization in membrane potential by Cs+ are caused by blockage of if but not by stimulation of the Na(+)-K+ pump and that if is an important source of Na+ loading into cells.

Cycle length effect on restitution of action potential duration in dog cardiac fibers

1983 ◽  
Vol 244 (6) ◽  
pp. H782-H792 ◽  
Author(s):  
V. Elharrar ◽  
B. Surawicz
Keyword(s):  
Steady State ◽  
Action Potential ◽  
Action Potential Duration ◽  
Fiber Types ◽  
Ventricular Muscle ◽  
Purkinje Fibers ◽  
Hyperbolic Curve ◽  
Cycle Lengths ◽  
Kinetics Of ◽  
State Curve

Electrical restitution of action potential duration (APD) was determined in Purkinje (n = 8) and ventricular muscle (n = 6) fibers at two different basic cycle lengths (BCL, 1,500 and 500 ms). Restitution curves, normalized for the longest APD (the plateau of restitution), fitted the sum of a fast (T1) and a slow (T2) exponential component. The T1 was shorter in ventricular muscle than Purkinje fibers (89 +/- 5 and 143 +/- 9; mean +/- SE, P less than 0.05), whereas the T2 did not differ (1,448 +/- 231 and 1,439 +/- 211). The BCL altered the APD value during the plateau of restitution but did not change the two exponential components. In both fiber types, the relation between APD and BCL during steady state fitted a hyperbolic curve that predicts the achievement of the maximum APD at long BCL. The restitution curves crossed the steady-state curve at two points outlining three different zones of APD intervals: early premature, late premature, and postmature. The APD during restitution was longer than the steady state in the late premature zone and shorter than the steady-state APD in the post-mature and early premature zones. The APD per se, independent of BCL, did not influence the kinetics of restitution in Purkinje fibers.

Rat vs. rabbit ventricle: Ca flux and intracellular Na assessed by ion-selective microelectrodes

1989 ◽  
Vol 256 (4) ◽  
pp. C813-C822 ◽  
Author(s):  
M. J. Shattock ◽  
D. M. Bers
Keyword(s):  
Steady State ◽  
Action Potential ◽  
Action Potential Duration ◽  
Resting Membrane Potential ◽  
Force Frequency ◽  
Functional Differences ◽  
Rest Periods ◽  
Net Uptake ◽  
Rat Ventricle ◽  
Cellular Ca

Trans sarcolemmal Ca movements in rabbit and rat ventricular muscle were compared using extracellular double-barreled Ca-selective microelectrodes. In rabbit ventricle, steady-state twitches were associated with transient extracellular Ca (Cao) depletions, indicative of Ca uptake during the twitch. In contrast, steady-state twitches in rat ventricle were associated with net cellular Ca extrusion. Rest periods in rabbit ventricle lead to a net loss of cell Ca and resumption of stimulation induces a net uptake of Ca by the cells. Conversely, in rat ventricle rest periods lead to cellular Ca gain and resumption of stimulation induces a net Ca loss from the cells. Thus stimulation is associated with net Ca gain in rabbit ventricle and net Ca loss in rat ventricle. These observations provide an explanation for some of the functional differences between rat and rabbit ventricle (e.g., negative force-frequency staircase and rest potentiation in rat vs. positive staircase and rest decay in rabbit). Resting intracellular Na activity (alpha iNa) was 12.7 +/- 0.6 mM in rat and 7.2 +/- 0.5 mM in rabbit ventricle. This alpha iNa in rat ventricle is sufficiently high that Ca entry via Na-Ca exchange is thermodynamically favored at the resting membrane potential. This may explain why rest potentiation is observed in rat ventricle. In contrast, the lower alpha iNa in rabbit ventricle would favor Ca extrusion via Na-Ca exchange at rest (and consequent rest decay). In rat ventricle, the increase of intracellular [Ca] ([Ca]i) associated with contraction, coupled with the short action potential duration, strongly favor Ca extrusion via Na-Ca exchange and explain the observed Cao accumulation observed during twitches in rat. The high plateau of the rabbit ventricular action potential tends to prevent Ca extrusion via Na-Ca exchange during the contraction and explains the Cao depletions observed in rabbit. It is concluded that the higher alpha iNa and shorter action potential duration in rat vs. rabbit ventricle can explain many of the functional differences observed in these tissues.

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