Mitochondria-Derived Ros Disturb Ca2+ Cycling and Evoke Abnormal Action Potentials in Guinea-Pig Ventricular Myocytes: A Theoretical Study

To explore a possible ionic basis for the prolonged Q-T interval in women compared with that in men, we investigated the electrophysiological effects of estrogen in isolated guinea pig ventricular myocytes. Action potentials and membrane currents were recorded using the whole cell configuration of the patch-clamp technique. Application of 17β-estradiol (10–30 μM) significantly prolonged the action potential duration (APD) at 20% (APD20) and 90% repolarization (APD90) at stimulation rates of 0.1–2.0 Hz. In the presence of 30 μM 17β-estradiol, APD20 and APD90 at 0.1 Hz were prolonged by 46.2 ± 17.1 and 63.4 ± 11.7% of the control ( n = 5), respectively. In the presence of 30 μM 17β-estradiol the peak inward Ca2+ current ( I CaL) was decreased to 80.1 ± 2.5% of the control ( n = 4) without a shift in its voltage dependence. Application of 30 μM 17β-estradiol decreased the rapidly activating component of the delayed outward K+ current ( I Kr) to 63.4 ± 8% and the slowly activating component ( I Ks) to 65.8 ± 8.7% with respect to the control; the inward rectifier K+ current was barely affected. The results suggest that 17β-estradiol prolonged APD mainly by inhibiting the I Kcomponents I Krand I Ks.

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Effects of BDF 9198 on action potentials and ionic currents from guinea-pig isolated ventricular myocytes

British Journal of Pharmacology ◽

10.1038/sj.bjp.0703476 ◽

2000 ◽

Vol 130 (8) ◽

pp. 1753-1766 ◽

Cited By ~ 21

Author(s):

K H Yuill ◽

M K Convery ◽

P C Dooley ◽

S A Doggrell ◽

J C Hancox

Keyword(s):

Guinea Pig ◽

Action Potentials ◽

Ventricular Myocytes ◽

Ionic Currents ◽

Isolated Ventricular Myocytes

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The effects of ryanodine, EGTA and low-sodium on action potentials in rat and guinea-pig ventricular myocytes: evidence for two inward currents during the plateau

British Journal of Pharmacology ◽

10.1111/j.1476-5381.1984.tb10107.x ◽

1984 ◽

Vol 81 (3) ◽

pp. 543-550 ◽

Cited By ~ 76

Author(s):

Mary R. Mitchell ◽

T. Powell ◽

D.A. Terrar ◽

V.W. Twist

Keyword(s):

Guinea Pig ◽

Action Potentials ◽

Ventricular Myocytes ◽

Low Sodium ◽

Inward Currents

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Mechanisms underlying the modulation of arrhythmogenic events by components of ischemia in guinea pig cardiac myocytes

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y94-056 ◽

1994 ◽

Vol 72 (4) ◽

pp. 382-393 ◽

Cited By ~ 1

Author(s):

Qi-Ying Liu ◽

Mario Vassalle

Keyword(s):

Guinea Pig ◽

Action Potential ◽

Voltage Clamp ◽

Action Potentials ◽

Ventricular Myocytes ◽

Resting Potential ◽

Spontaneous Discharge ◽

High K ◽

Voltage Dependent ◽

Dependent Mechanism

The effects of some components of ischemia on the oscillatory (Vos) and nonoscillatory (Vex) potentials and respective currents (Ios and Iex), as well as their mechanisms, were studied in guinea pig isolated ventricular myocytes by means of a single-microelectrode, discontinuous voltage clamp method. Repetitive activations induced not only Vos and Ios, but also Vex and Iex. A small decrease in resting potential caused an immediate increase in Vos followed by a gradual increase due to the longer action potential. Immediate and gradual increases in Ios also occurred during voltage clamp steps. A small depolarization increased Vos and Vex, and facilitated the induction of spontaneous discharge by fast drive. At Vh where INa is inactivated, depolarizing steps induced larger Ios and Iex, indicating the importance of the Na-independent Ca loading. High [K]odecreased the resting potential, but also Vos, Vex, Ios, Iex, and ICa. In high [K]o, depolarization still increased Vos and Vex. Norepinephrine (NE) enhanced Vos and Vex, and also Ios and Iex, during voltage clamp steps. High [K]o antagonized NE effects, and NE those of high [K]o. In conclusion, on depolarization, Vos and Ios immediately increase through a voltage-dependent mechanism; and then Vos and Ios gradually increase, apparently through an increased Ca load related to the longer action potentials and the Na–Ca exchange. The depolarization induced by Vex may contribute to increase Vos size. Vos and Vex are similarly influenced by different procedures that modify Ca load. The arrhythmogenic events are enhanced by the simultaneous presence of depolarization, faster rate, or NE. Instead, high [K]o decreases Vos and Vex by decreasing ICa and opposes the effects of NE. The voltage clamp results show that potentiation and antagonism between different components of ischemia are due primarily to changes in Ca loading and not to changes in action potential configuration.Key words: ischemia, arrhythmias, oscillatory and nonoscillatory potentials and currents, norepinephrine, potassium.

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L-364,373 (R-L3) enantiomers have opposite modulating effects on IKs in mammalian ventricular myocytes

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2012-0407 ◽

2013 ◽

Vol 91 (8) ◽

pp. 586-592 ◽

Cited By ~ 1

Author(s):

Claudia Corici ◽

Zsófia Kohajda ◽

Attila Kristóf ◽

András Horváth ◽

László Virág ◽

...

Keyword(s):

Patch Clamp ◽

Guinea Pig ◽

Action Potential ◽

Right Ventricular ◽

Action Potential Duration ◽

Action Potentials ◽

Ventricular Arrhythmias ◽

Ventricular Myocytes ◽

Delayed Rectifier ◽

Whole Cell Patch Clamp

Activators of the slow delayed rectifier K+ current (IKs) have been suggested as promising tools for suppressing ventricular arrhythmias due to prolongation of repolarization. Recently, L-364,373 (R-L3) was nominated to activate IKs in myocytes from several species; however, in some studies, it failed to activate IKs. One later study suggested opposite modulating effects from the R-L3 enantiomers as a possible explanation for this discrepancy. Therefore, we analyzed the effect of the RL-3 enantiomers on IKs in ventricular mammalian myocytes, by applying standard microelectrode and whole-cell patch-clamp techniques at 37 °C. We synthesized 2 substances, ZS_1270B (right) and ZS_1271B (left), the 2 enantiomers of R-L3. In rabbit myocytes, ZS_1270B enhanced the IKs tail current by approximately 30%, whereas ZS_1271B reduced IKs tails by 45%. In guinea pig right ventricular preparations, ZS_1270B shortened APD90 (action potential duration measured at 90% repolarization) by 12%, whereas ZS_1271B lengthened it by approximately 15%. We concluded that R-L3 enantiomers in the same concentration range indeed have opposite modulating effects on IKs, which may explain why the racemic drug R-L3 previously failed to activate IKs. ZS_1270B is a potent IKs activator, therefore, this substance is appropriate to test whether IKs activators are ideal tools to suppress ventricular arrhythmias originating from prolongation of action potentials.

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Effects of chromanol 239b on I Ks and action potentials of guinea pig ventricular myocytes

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(98)80402-6 ◽

1998 ◽

Vol 31 ◽

pp. 471-472

Author(s):

J. Schreieck ◽

Y. Wang ◽

B. Zrenner ◽

A. Schörnig ◽

C. Schmitt

Keyword(s):

Guinea Pig ◽

Action Potentials ◽

Ventricular Myocytes

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Myocardial Depressant Effects of Desflurane

Anesthesiology ◽

10.1097/01.anes.0000265155.01815.6d ◽

2007 ◽

Vol 106 (5) ◽

pp. 956-966 ◽

Cited By ~ 11

Author(s):

Wyun Kon Park ◽

Myung Hee Kim ◽

Duck Sun Ahn ◽

Jee Eun Chae ◽

Young Seok Jee ◽

...

Keyword(s):

Sarcoplasmic Reticulum ◽

Guinea Pig ◽

Action Potentials ◽

Ventricular Myocytes ◽

Isometric Force ◽

Peak Force ◽

Papillary Muscles ◽

Tyrode Solution ◽

Rapid Cooling ◽

K Current

Background The authors determined whether desflurane altered myocardial excitation-contraction coupling and electrophysiologic behavior in the same manner as isoflurane and sevoflurane. Methods The effects of desflurane on isometric force in guinea pig ventricular papillary muscles were studied in modified standard and in 26 mM K(+) Tyrode solution with 0.1 microm isoproterenol. Desflurane effects on sarcoplasmic reticulum Ca(2+) release were also determined by examining its actions on rat papillary muscles, guinea pig papillary muscles in low-Na(+) Tyrode solution, and rapid cooling contractures. Normal and slow action potentials were recorded using a conventional microelectrode technique. Ca(2+) and K(+) currents of guinea pig ventricular myocytes were examined. Results Desflurane (5.3% and 11.6%) decreased peak force to approximately 70% and 40% of the baseline, respectively, similar to the effects of equianesthetic isoflurane concentrations. With isoproterenol in 26 mM K(+) Tyrode solution, desflurane markedly depressed late peaking force and modestly depressed early peak force. The rested state contractions of rat myocardium or guinea pig myocardium in low-Na(+) Tyrode solution were modestly depressed, whereas rapid cooling contractures were virtually abolished after desflurane administration. Desflurane significantly prolonged the action potential duration. Desflurane reduced L-type Ca(2+) current and the delayed outward K(+) current but did not alter the inward rectifier K(+) current. Conclusions Myocardial depression by desflurane is due to decreased Ca(2+) influx, whereas depolarization-activated sarcoplasmic reticulum Ca(2+) release is modestly depressed, similar to the actions of isoflurane and sevoflurane. Desflurane depressed the delayed outward K(+) current associated with significant lengthening of cardiac action potentials.

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