Ca2+ influx induced by the agonist U46619 is inhibited by hyperpolarization induced by the K+ channel opener cromakalim in canine coronary artery.
The fura-2 microscopic fluorimetric method was used to examine the effects of the thromboxane A2 analogue, U46619, on the force of contraction and intracellular calcium concentrations ([Ca2+]i) in canine coronary arteries. Upon cumulative application, U46619 increased [Ca2+]i and force. Depolarization by 20 mM KCl potentiated the increase in [Ca2+]i and increased the maximum force induced by U46619. In 5 mM KCl-PSS, the reduction of resting [Ca2+]i by cromakalim (3 x 10(-6) M) was greater than that by verapamil (3 x 10(-6) M). Cromakalim and verapamil inhibited the increases in [Ca2+]i and force induced by U46619 in 5 mM KCl-PSS. In 90 mM KCl-PSS in the presence of U46619, verapamil inhibited the increases in [Ca2+]i and force, whereas cromakalim did not inhibit them at all. The inhibitory effect of cromakalim was counteracted by depolarization by 20 or 25 mM KCl. Curves in the presence of U46619 which related force to [Ca2+]i were shifted to the left compared with that in the absence of U46619, suggesting that U46619 increases the Ca(2+)-sensitivity of the contractile proteins. Thus, U46619 produces Ca2+ influx through L-type Ca2+ channels, which are deactivated by hyperpolarization induced by cromakalim.
Yamagishi
T
T
Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
Yanagisawa
T
T
Taira
N
N
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D019806:Cromakalim; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005453:Fluorescence; D066298:In Vitro Techniques; D008297:Male; D015221:Potassium Channels / Q000187:drug effects*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D001578:Benzopyrans; D015221:Potassium Channels; D011450:Prostaglandin Endoperoxides, Synthetic; D011758:Pyrroles; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019806:Cromakalim; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D014700:Verapamil; D002118:Calcium