Paradoxical Effect of Dofetilide on Action Potential Duration and Calcium Transient Amplitude in Newborn Rabbit Ventricular Myocytes

2005 ◽  
Vol 45 (2) ◽  
pp. 165-174 ◽  
Author(s):  
Shekhar Srivastava ◽  
Leon Collis ◽  
Anita Go ◽  
Salvatore Mancarella ◽  
William A Coetzee ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Ventricular Myocytes ◽  
Calcium Transient ◽  
Paradoxical Effect ◽  
Newborn Rabbit ◽  
Rabbit Ventricular Myocytes

Biphasic effects of cell volume on excitation-contraction coupling in rabbit ventricular myocytes

2002 ◽  
Vol 282 (4) ◽  
pp. H1270-H1277 ◽  
Author(s):  
Gui-Rong Li ◽  
Min Zhang ◽  
Leslie S. Satin ◽  
Clive M. Baumgarten
Keyword(s):  
Action Potential ◽  
Cell Volume ◽  
Action Potential Duration ◽  
Ventricular Myocytes ◽  
Current Clamp ◽  
Osmotic Swelling ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Fura 2 ◽  
Rabbit Ventricular Myocytes

We studied the effects of osmotic swelling on the components of excitation-contraction coupling in ventricular myocytes. Myocyte volume rapidly increased 30% in hyposmotic (0.6T) solution and was constant thereafter. Cell shortening transiently increased 31% after 4 min in 0.6T but then decreased to 68% of control after 20 min. In parallel, the L-type Ca2+ current ( I Ca-L) transiently increased 10% and then declined to 70% of control. Similar biphasic effects on shortening were observed under current clamp. In contrast, action potential duration was unchanged at 4 min but decreased to 72% of control after 20 min. Ca2+ transients were measured with fura 2-AM. The emission ratio with excitation at 340 and 380 nm (f340/f380) decreased by 12% after 3 min in 0.6T, whereas shortening and I Ca-L increased at the same time. After 8 min, shortening, I Ca-L, and the f340/f380 ratio decreased 28, 25, and 59%, respectively. The results suggest that osmotic swelling causes biphasic changes in I Ca-L that contribute to its biphasic effects on contraction. In addition, swelling initially appears to reduce the Ca2+ transient initiated by a given I Ca-L, and later, both I Ca-L and the Ca2+ transient are inhibited.

scholarly journals Action Potential Duration Restitution and Alternans in Rabbit Ventricular Myocytes

2005 ◽  
Vol 96 (4) ◽  
pp. 459-466 ◽  
Author(s):  
Joshua I. Goldhaber ◽  
Lai-Hua Xie ◽  
Tan Duong ◽  
Christi Motter ◽  
Kien Khuu ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Ventricular Myocytes ◽  
Rabbit Ventricular Myocytes ◽  
Action Potential Duration Restitution

Dual effects of external magnesium on action potential duration in guinea pig ventricular myocytes

1995 ◽  
Vol 268 (6) ◽  
pp. H2321-H2328 ◽  
Author(s):  
S. Zhang ◽  
T. Sawanobori ◽  
H. Adaniya ◽  
Y. Hirano ◽  
M. Hiraoka
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Decay Time ◽  
Action Potential Duration ◽  
Time Course ◽  
Ventricular Myocytes ◽  
Membrane Surface ◽  
Surface Charges ◽  
Whole Cell Patch Clamp ◽  
K Current

Effects of extracellular magnesium (Mg2+) on action potential duration (APD) and underlying membrane currents in guinea pig ventricular myocytes were studied by using the whole cell patch-clamp method. Increasing external Mg2+ concentration [Mg2+]o) from 0.5 to 3 mM produced a prolongation of APD at 90% repolarization (APD90), whereas 5 and 10 mM Mg2+ shortened it. [Mg2+]o, at 3 mM or higher, suppressed the delayed outward K+ current and the inward rectifier K+ current. Increases in [Mg2+]o depressed the peak amplitude and delayed the decay time course of the Ca2+ current (ICa), the latter effect is probably due to the decrease in Ca(2+)-induced inactivation. Thus 3 mM Mg2+ suppressed the peak ICa but increased the late ICa amplitude at the end of a 200-ms depolarization pulse, whereas 10 mM Mg2+ suppressed both components. Application of 10 mM Mg2+ shifted the voltage-dependent activation and inactivation by approximately 10 mV to more positive voltage due to screening the membrane surface charges. Application of manganese (1-5 mM) also caused dual effects on APD90, similar to those of Mg2+, and suppressed the peak ICa with slowed decay. These results suggest that the dual effects of Mg2+ on APD in guinea pig ventricular myocytes can be, at least in part, explained by its action on ICa with slowed decay time course in addition to suppressive effects on K+ currents.

Droperidol Inhibits Intracellular Ca2+, Myofilament Ca2+Sensitivity, and Contraction in Rat Ventricular Myocytes

2005 ◽  
Vol 102 (6) ◽  
pp. 1165-1173 ◽  
Author(s):  
Toshiya Shiga ◽  
Sandro Yong ◽  
Joseph Carino ◽  
Paul A. Murray ◽  
Derek S. Damron
Keyword(s):  
Nitric Oxide ◽  
Action Potential ◽  
Action Potential Duration ◽  
Ventricular Myocytes ◽  
Nitric Oxide Production ◽  
Cellular Mechanisms ◽  
Rat Ventricular Myocytes ◽  
Oxide Production ◽  
Perfused Hearts ◽  
Ca Sensitivity

Background Droperidol has recently been associated with cardiac arrhythmias and sudden cardiac death. Changes in action potential duration seem to be the cause of the arrhythmic behavior, which can lead to alterations in intracellular free Ca concentration ([Ca]i). Because [Ca]i and myofilament Ca sensitivity are key regulators of myocardial contractility, the authors' objective was to identify whether droperidol alters [Ca]i or myofilament Ca sensitivity in rat ventricular myocytes and to identify the cellular mechanisms responsible for these effects. Methods Freshly isolated rat ventricular myocytes were obtained from adult rat hearts. Myocyte shortening, [Ca]i, nitric oxide production, intracellular pH, and action potentials were monitored in cardiomyocytes exposed to droperidol. Langendorff perfused hearts were used to assess overall cardiac function. Results Droperidol (0.03-1 mum) caused concentration-dependent decreases in peak [Ca]i and shortening. Droperidol inhibited 35 mm KCl-induced increase in [Ca]i, with little direct effect on sarcoplasmic reticulum Ca stores. Droperidol had no effect on action potential duration but caused a rightward shift in the concentration-response curve to extracellular Ca for shortening, with no concomitant effect on peak [Ca]i. Droperidol decreased pHi and increased nitric oxide production. Droperidol exerted a negative inotropic effect in Langendorff perfused hearts. Conclusion These data demonstrate that droperidol decreases cardiomyocyte function, which is mediated by a decrease in [Ca]i and a decrease in myofilament Ca sensitivity. The decrease in [Ca]i is mediated by decreased sarcolemmal Ca influx. The decrease in myofilament Ca sensitivity is likely mediated by a decrease in pHi and an increase in nitric oxide production.

Mechanical and electrophysiological effects of a hydroxyphenyl-substituted tetrahydroisoquinoline, SL-1, on isolated rat cardiac tissues

1995 ◽  
Vol 73 (11) ◽  
pp. 1651-1660 ◽  
Author(s):  
Gwo-Jyh Chang ◽  
Ming-Jai Su ◽  
Pei-Hong Lee ◽  
Shoei-Sheng Lee ◽  
Karin Chiung-Sheue Liu
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Positive Inotropic Effect ◽  
Ventricular Myocytes ◽  
Inotropic Effect ◽  
Dependent Manner ◽  
Cardiac Tissues ◽  
Inward Current ◽  
Adrenoceptor Antagonist ◽  
Isolated Rat

The mechanisms of the positive inotropic action of a new synthetic tetrahydroisoquinoline compound, SL-1, were investigated in isolated rat cardiac tissues and ventricular myocytes. SL-1 produced a rapidly developing, concentration-dependent positive inotropic response in both atrial and ventricular muscles and a negative chronotropic effect in spontaneously beating right atria. The positive inotropic effect was not prevented by pretreatment with reserpine (3 mg/kg) or the α-adrenoceptor antagonist prazosin (1 μM), but was suppressed by either the β-adrenoceptor antagonist atenolol (3 μM) or the K+ channel blocker 4-aminopyridine (4AP, 1 mM). In the whole-cell recording study, SL-1 increased the plateau level and prolonged the action potential duration in a concentration-dependent manner and decreased the maximum upstroke velocity [Formula: see text] and amplitude of the action potential in isolated rat ventricular myocytes stimulated at 1.0 Hz. On the other hand, SL-1 had little effect on the resting membrane potential, although it caused a slight decrease at higher concentrations. Voltage clamp experiments revealed that the increase of action potential plateau and prolongation of action potential duration were associated with an increase of Ca2+ inward current (ICa) via the activation of β-adrenoceptors and a prominent inhibition of 4AP-sensitive transient outward K+ current (Ito) with an IC50 of 3.9 μM. Currents through the inward rectifier K+ channel (IKl) were also reduced. The inhibition of Ito is characterized by a reduction in peak amplitude and a marked acceleration of current decay but without changes on the voltage dependence of steady-state inactivation. In addition to the inhibition of K+ currents, SL-1 also inhibited the Na+ inward current (INa) with an IC50 of 5.4 μM, which was correlated with the decrease of [Formula: see text]. We conclude that the positive inotropic effect of SL-1 may be due to an increase in Ca2+ current mediated via partial activation of β-adrenoceptors and an inhibition of K+ outward currents and the subsequent prolongation of action potentials.Key words: SL-1, tetrahydroisoquinoline, inotropic and chronotropic action, action potential, Na+, Ca2+, and K+ currents.

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