Effects of K+ Channel Modulators on the Relationship Between Action Potential Duration and Ca2+ Transients in Single Ventricular Myocytes of the Guinea Pig

Effects of K+ channel modulators, cromakalim and E4031 [1-[2-(6-methyl-2-pyridyl)-ethyl]-4-(4-methylsulfonylaminobenzoyl) piperidine], on the relationship between the action potential duration (APD) and Ca2+ transients were examined in single myocytes isolated from guinea pig cardiac left ventricle....

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Bibliographic Details
Published in:Japanese Journal of Pharmacology 1999, Vol.80(3), pp.243-253
Main Authors: Tokuno, Tomoaki, Muraki, Katsuhiko, Watanabe, Minoru, Imaizumi, Yuji
Format: Article
Language:eng ; jpn
Subjects:
Action Potentials - drug effects
Animals
Anti-Arrhythmia Agents - pharmacology
Arrhythmias, Cardiac - physiopathology
Arrhythmias, Cardiac - prevention & control
Ca2+ transient
Calcium - metabolism
Cromakalim
Cromakalim - pharmacology
E4031
Glyburide - pharmacology
Guinea Pigs
Heart
Heart Ventricles - cytology
Heart Ventricles - drug effects
Hypoglycemic Agents - pharmacology
K+ channel
Male
Patch-Clamp Techniques
Piperidines - pharmacology
Potassium Channel Blockers
Pyridines - pharmacology
Time Factors
Vasodilator Agents - pharmacology
Ventricular Function
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Summary:Effects of K+ channel modulators, cromakalim and E4031 [1-[2-(6-methyl-2-pyridyl)-ethyl]-4-(4-methylsulfonylaminobenzoyl) piperidine], on the relationship between the action potential duration (APD) and Ca2+ transients were examined in single myocytes isolated from guinea pig cardiac left ventricle. Application of cromakalim decreased APD at 90% repolarization (APD90) and Ca2+ transient elicited at 0.5 Hz (IC50s=0.6 and 3 μM, respectively). Application of 0.3 μM E4031 increased these parameters by 110% and 45%, respectively. Under voltage-clamp, the relation between the duration of depolarization to OmV and Ca2+ transients could be described by the sum of two exponential components; the time constants were approximately 5 and 280 msec, respectively. The first component was abolished by 10 μM ryanodine, suggesting the involvement of Ca2+-induced Ca2+ release (CICR). Neither cromakalim nor E4031 directly affected Ca2+ current and Ca2+ transients under voltage clamp. When APD was changed by K+ channel modulators, the relation between APD90 and Ca2+-transients was almost similar to that obtained by changing the depolarization duration under voltage-clamp. CICR was changed significantly only when APD90 was markedly shortened by cromakalim. The extensively prolonged AP and Ca2+ transient in the presence of E4031 were reduced by an addition of cromakalim. It is concluded that these two K+ channel modulators can significantly alter the AP-induced Ca2+ transient mainly by changing APD, which regulates both Ca2+ influx and extrusion.
ISSN:0021-5198
1347-3506
DOI:10.1254/jjp.80.243