Increased Nav 1.5 channel late current underlies prolongation of action potential duration of ventricular myocytes from aged guinea pigs

Heart Rhythm ◽  
2013 ◽  
Vol 10 (11) ◽  
pp. 1748-1749
Author(s):  
Y. Song ◽  
J.C. Shryock ◽  
L. Belardinelli
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Guinea Pigs ◽  
Ventricular Myocytes ◽  
Prolongation Of Action Potential

scholarly journals Enhanced basal late sodium current appears to underlie the age-related prolongation of action potential duration in guinea pig ventricular myocytes

2018 ◽  
Vol 125 (4) ◽  
pp. 1329-1338
Author(s):  
Yejia Song ◽  
Luiz Belardinelli
Keyword(s):  
Oxidative Stress ◽  
Action Potential ◽  
Action Potential Duration ◽  
Guinea Pigs ◽  
Qt Interval ◽  
Ventricular Myocytes ◽  
Sodium Current ◽  
Late Sodium Current ◽  
Age Related ◽  
Prolongation Of Action Potential

Aging hearts have prolonged QT interval and are vulnerable to oxidative stress. Because the QT interval indirectly reflects the action potential duration (APD), we examined the hypotheses that 1) the APD of ventricular myocytes increases with age; 2) the age-related prolongation of APD is due to an enhancement of basal late Na+ current ( INaL); and 3) inhibition of INaL may protect aging hearts from arrhythmogenic effects of hydrogen peroxide (H2O2). Experiments were performed on ventricular myocytes isolated from (young) 1-mo- and (old) 1-yr-old guinea pigs (GPs). The APD of myocytes from old GPs was significantly longer than that from young GPs and was shortened by the INaL inhibitors GS967 and tetrodotoxin. The magnitude of INaL was significantly larger in myocytes from old than from young GPs. The CaMKII inhibitors KN-93 and AIP and the NaV1.5-channel blocker methanethiosulfonate ethylammonium blocked the INaL. There were no significant differences between myocytes from young and old GPs in L-type Ca2+ current and the rapidly and slowly activating delayed rectifier K+ currents, although the inward rectifier K+ current was slightly decreased in myocytes from old GPs. H2O2 induced more early afterdepolarizations in myocytes from old than from young GPs. The effect of H2O2 was attenuated by GS967. The results suggest that 1) the APD of myocytes from old GPs is prolonged, 2) a CaMKII-mediated increase in NaV1.5-channel INaL is responsible for the prolongation of APD, and 3) inhibition of INaL may be beneficial for maintaining electrical stability under oxidative stress in myocytes of old GPs. NEW & NOTEWORTHY The action potential duration is significantly longer in ventricular myocytes from old than from young guinea pigs, which may explain, at the cellular level, the increase in QT interval with age. A CaMKII-mediated enhancement of NaV1.5-channel late current is responsible for the age-related prolongation of action potential duration. The enhanced basal late sodium current may predispose cardiac myocytes of old animals to oxidative stress and arrhythmogenesis.

Electrophysiologic Effect of Desflurane on the Prolongation of Action Potential Duration in Ventricular Myocytes

2006 ◽  
Vol 50 (5) ◽  
pp. 557
Author(s):  
Sun Jun Bae ◽  
Myung Hee Kim ◽  
Jee Eun Chae ◽  
Chong Hoon Kim ◽  
Kyung Tae Min ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Ventricular Myocytes ◽  
Prolongation Of Action Potential

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.

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