Extracellular potassium dependent negative dromotropic action of nicorandil in guinea pig myocardium.
Although the antiarrhythmic action of nicorandil is drawing an increasing attention, dromotropic effect of this agent is unclear. Therefore, this was investigated by microelectrode technique to the superfused guinea pig papillary muscle to record the action potential and extracellular potential during conduction. The correlation of myocardial internal longitudinal resistance (r1) assumed to reflect the global gap junctional resistance, maximum rate of rise of the action potential upstroke (Vmax), and conduction velocity was examined under the alterations of external potassium concentrations ([K+]e; ranging from 3.0 to 12.0 mM) in the presence or absence of 100 microM nicorandil. In the minimum [K+]e, nicorandil caused significant (p < 0.05) hyperpolarization and reduction in Vmax. Negative dromotropic action of nicorandil was slight but significant (p < 0.05) in low (3.0 mM) [K+]e but was not evident in physiologic (5.4 mM) or elevated (9.0 to 12.0 mM)[K+]e. In conclusion, nicorandil exerts negative dromotropic action as [K+]e decreased, which was accounted for by the cable analysis and may contribute to the prevention of low [K+]e-induced arrhythmia.
Kuma
Fumiaki
F
Department of Biosystemic Science and Medicine, Kyushu University, Graduate School of Medical Sciences, Fukuoka 812-8582, Japan.
Maruyama
Toru
T
Ito
Hiroyuki
H
Kaji
Yoshikazu
Y
Harada
Mine
M
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D005110:Extracellular Space; D006168:Guinea Pigs; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D020108:Nicorandil / Q000494:pharmacology*; D011188:Potassium / Q000502:physiology*
D000889:Anti-Arrhythmia Agents; D020108:Nicorandil; D011188:Potassium