Effects of Ca2+ channel antagonists and ryanodine on H1-receptor mediated electromechanical response to histamine in guinea-pig left atria.
Effects of organic Ca2+ channel antagonists, Ni2+ and ryanodine on the electrophysiological and positive inotropic responses to histamine were examined in isolated guinea-pig left atria. Histamine increased force of contraction, prolonged action potential duration (APD) and hyperpolarized the membrane in a concentration-dependent manner. Histamine at a concentration of 1 mumol/l produced a dual-component positive inotropic response composed of an initial increasing phase (initial component) and a second and late developing, greater positive inotropic phase (second component), whereas causing monophasic changes in APD and resting potential. The electrophysiological and dual-component positive inotropic effects induced by histamine were antagonized by chlorpheniramine (1 mumol/l) but not by cimetidine (10 mumol/l), indicating that both effects are exclusively mediated by H1-receptors. The positive inotropic response to 1 mumol/l histamine was changed by the pretreatment with nifedipine (1 mumol/l) and nisoldipine (1 mumol/l). In the presence of these dihydropyridines, the second component was almost completely abolished, while the initial component was hardly affected. On the other hand, verapamil (3 mumol/l) and diltiazem (10 mumol/l) failed to modify the multiphasic inotropic response to histamine. None of the Ca2+ channel antagonists affected the histamine-induced APD prolongation. In the presence of Ni2+ at a concentration of 0.3 mmol/l, at which it produced no negative inotropic action, the second component of the positive inotropic effect of histamine was specifically suppressed whereas the histamine-induced APD prolongation was unaffected. Preferential attenuation of the second component was also observed in the presence of 30 nmol/l ryanodine.(ABSTRACT TRUNCATED AT 250 WORDS)
Hattori
Y
Y
Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
Nakaya
H
H
Tohse
N
N
Kanno
M
M
D000200:Action Potentials / Q000187:drug effects; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009532:Nickel / Q000494:pharmacology; D011968:Receptors, Histamine / Q000187:drug effects*; D011969:Receptors, Histamine H1 / Q000187:drug effects*; D012433:Ryanodine / Q000494:pharmacology*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism
D000470:Alkaloids; D002121:Calcium Channel Blockers; D011968:Receptors, Histamine; D011969:Receptors, Histamine H1; D012433:Ryanodine; D009532:Nickel; D006632:Histamine; D002118:Calcium