Prolongation of Action Potential Duration and QT Interval During Epilepsy Linked to Increased Contribution of Neuronal Sodium Channels to Cardiac Late Na + Current

2015 ◽  
Vol 8 (4) ◽  
pp. 912-920 ◽  
Author(s):  
Michael Biet ◽  
Nathalie Morin ◽  
Melissa Lessard-Beaudoin ◽  
Rona K. Graham ◽  
Sandra Duss ◽  
...  
Keyword(s):  
Action Potential ◽  
Sodium Channels ◽  
Action Potential Duration ◽  
Qt Interval ◽  
Na Current ◽  
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.

Sprint training shortens prolonged action potential duration in postinfarction rat myocyte: mechanisms

2001 ◽  
Vol 90 (5) ◽  
pp. 1720-1728 ◽  
Author(s):  
Xue-Qian Zhang ◽  
Lian-Qin Zhang ◽  
Bradley M. Palmer ◽  
Yuk-Chow Ng ◽  
Timothy I. Musch ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Outward Current ◽  
Activation Parameters ◽  
Resting Membrane Potential ◽  
Transient Outward Current ◽  
Sprint Training ◽  
Myocyte Hypertrophy ◽  
Dependent Inactivation ◽  
Prolongation Of Action Potential

Two electrophysiological manifestations of myocardial infarction (MI)-induced myocyte hypertrophy are prolongation of action potential duration (APD) and reduction of transient outward current ( I to) density. Because high-intensity sprint training (HIST) ameliorated myocyte hypertrophy and improved myocyte Ca2+ homeostasis and contractility after MI, the present study evaluated whether 6–8 wk of HIST would shorten the prolonged APD and improve the depressed I to in post-MI myocytes. There were no differences in resting membrane potential and action potential amplitude (APA) measured in myocytes isolated from sham-sedentary (Sed), MI-Sed, and MI-HIST groups. Times required for repolarization to 50 and 90% APA were significantly ( P < 0.001) prolonged in MI-Sed myocytes. HIST reduced times required for repolarization to 50 and 90% APA to values observed in Sham-Sed myocytes. The fast and slow components of I towere significantly ( P < 0.0001) reduced in MI-Sed myocytes. HIST significantly ( P < 0.001) enhanced the fast and slow components of I to in MI myocytes, although not to levels observed in Sham-Sed myocytes. There were no significant differences in steady-state I toinactivation and activation parameters among Sham-Sed, MI-Sed, and MI-HIST myocytes. Likewise, recovery from time-dependent inactivation was also similar among the three groups. We suggest that normalization of APD after MI by HIST may be mediated by restoration of I to toward normal levels.

scholarly journals The p.P888L SAP97 polymorphism increases the transient outward current (Ito,f) and abbreviates the action potential duration and the QT interval

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
David Tinaquero ◽  
◽  
Teresa Crespo-García ◽  
Raquel G. Utrilla ◽  
Paloma Nieto-Marín ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Qt Interval ◽  
Outward Current ◽  
Transient Outward Current

Class III Antiarrhythmic Effects of Dofetilide in Rabbit Atrial Myocardium

1996 ◽  
Vol 1 (3) ◽  
pp. 229-234 ◽  
Author(s):  
Regan T. Pallandi ◽  
Nigel H. Lovell ◽  
Terence J. Campbell
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Interstimulus Interval ◽  
Class Iii ◽  
Atrial Myocardium ◽  
New Class ◽  
Class Iii Antiarrhythmic Agent ◽  
Prolongation Of Action Potential ◽  
Dose Dependent ◽  
Microelectrode Techniques

Background Dofetilide is a new class III antiarrhythmic agent with demonstrated efficacy in ventricular and atrial tachyarrhythmias. We investigated its class HI actions and their modulation by stimulation rate in rabbit atrial myocardium. Methods and Results Standard microelectrode techniques were used to record action potentials from rabbit atrial tissue at varying stimulation rates. Dofetilide produced a dose-dependent prolongation of action potential duration at concentrations from 1 nM to 1 μM at an interstimulus interval of 1000 ms. Action potential duration at 90% repolarization (action potential duration) was prolonged from 116 ± 11.7 ms in control solutions to 148 ± 13.9 ms at 1nM dofetilide and 186 ± 49.3 ms at 1 μM dofetilide ( P < .05 for 1 nM vs control; P < .01 for 1 μM vs control). Reduction of interstimulus interval to 500 ms had no significant effect on action potential duration prolongation by dofetilide. At faster rates than this, and particularly at an interstimulus interval less than 330 ms, a marked “reverse rate dependence” of the class III effect was observed. Specifically, the high therapeutic concentration of 10 nM showed no effect on action potential duration at interstimulus interval of 250 ms or 200 ms, and even at a concentration of 30 nM, the small class III effect was no longer statistically significant at these rates. Conclusion Dofetilide prolongs action potential duration in rabbit atrial myocardium, but this effect is significantly attenuated at stimulation rates above 2 Hz.

scholarly journals P6281A DLG1 polymorphism shortens the action potential duration and the QT interval

2017 ◽  
Vol 38 (suppl_1) ◽  
Author(s):  
E. Delpon ◽  
D. Tinaquero ◽  
S. Alfayate ◽  
P. Nieto-Marin ◽  
R.G. Utrilla ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Qt Interval

Exaggerated block of hERG (KCNH2) and prolongation of action potential duration by erythromycin at temperatures between 37°C and 42°C

Heart Rhythm ◽  
2005 ◽  
Vol 2 (8) ◽  
pp. 860-866 ◽  
Author(s):  
Jiqing Guo ◽  
Shu Zhan ◽  
James P. Lees-Miller ◽  
GuoQi Teng ◽  
Henry J. Duff
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Prolongation Of Action Potential

Alleviation of contractile dysfunction in ischemic hearts by slowly inactivating Na+ current blockers

1995 ◽  
Vol 269 (2) ◽  
pp. H533-H540 ◽  
Author(s):  
B. Le Grand ◽  
B. Vie ◽  
J. M. Talmant ◽  
E. Coraboeuf ◽  
G. W. John
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Diastolic Pressure ◽  
Systolic Function ◽  
Left Ventricular ◽  
Na Current ◽  
Drug Concentrations ◽  
Window Current ◽  
R 56865 ◽  
Reduced Action

We hypothesized that the slowly inactivating component of Na+ current, which is an integral part of the Na+ window current, is a major pathway for Na+ loading during myocardial ischemia. The putative protective effects of tetrodotoxin (TTX) and R-56865, at concentrations that selectively blocked the Na+ window current, as assessed by action potential plateau shortening without affecting maximum upstroke velocity (Vmax), were examined in isolated Langendorff-perfused guinea pig hearts subjected to 50 min of normothermic global ischemia and 60 min of reperfusion. In papillary muscles, TTX reduced action potential duration at > or = 10 nM but reduced Vmax only at > or = 1 microM. R-56865 (10 nM-10 microM) failed to affect Vmax but concentration dependently reduced action potential duration. Ischemia-induced cardiac dysfunction, including increases in left ventricular end-diastolic pressure and lactate dehydrogenase and creatine phosphokinase release at reperfusion, was attenuated by TTX and R-56865 (0.1-320 nM). Ischemic contracture (increase in left ventricular end-diastolic pressure) was abolished by drug concentrations as low as 1 nM, whereas higher concentrations (> 10 nM) of TTX and R-56865 were required to restore systolic function at reperfusion. TTX and R-56865 had little or no effect on hemodynamic variables. Evidence is provided of pronounced and direct cardioprotective effects of low concentrations of R-56865 and TTX in cardiac muscle during ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

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
Sign in / Sign up

Export Citation Format

Share Document