TY - JOUR
T1 - Ca2+ Influx Induced by the Agonist U46619 Is Inhibited by Hyperpolarization Induced by the K+ Channel Opener Cromakalim in Canine Coronary Artery
AU - Yamagishi, Toshio
AU - Yanagisawa, Teruyuki
AU - Taira, Norio
PY - 1992/7
Y1 - 1992/7
N2 - 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 KC1 potentiated the increase in [Ca2+]i and increased the maximum force induced by U46619. In 5 mM KC1-PSS, the reduction of resting [Ca2+]i by cromakalim (3 X 10-6 M) was greater than that by verapamil (3 X 10-6M). Cromakalim and verapamil inhibited the increases in [Ca2+]i and force induced by U46619 in 5 mM KC1-PSS. In 90 mM KC1-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 KC1. 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 Ca2+-sensitivity of the contractile proteins. Thus, U46619 produces Ca2+ influx through L-type Ca2+ channels, which are deactivated by hyperpolarization induced by cromakalim.
AB - 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 KC1 potentiated the increase in [Ca2+]i and increased the maximum force induced by U46619. In 5 mM KC1-PSS, the reduction of resting [Ca2+]i by cromakalim (3 X 10-6 M) was greater than that by verapamil (3 X 10-6M). Cromakalim and verapamil inhibited the increases in [Ca2+]i and force induced by U46619 in 5 mM KC1-PSS. In 90 mM KC1-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 KC1. 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 Ca2+-sensitivity of the contractile proteins. Thus, U46619 produces Ca2+ influx through L-type Ca2+ channels, which are deactivated by hyperpolarization induced by cromakalim.
KW - Ca2+ channels
KW - Cromakalim
KW - Intracellular calcium concentration
KW - K+ channels
KW - Thromboxane A2 analogue
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U2 - 10.1254/jjp.59.291
DO - 10.1254/jjp.59.291
M3 - Article
C2 - 1434126
AN - SCOPUS:0026616812
VL - 59
SP - 291
EP - 299
JO - Japanese Journal of Pharmacology
JF - Japanese Journal of Pharmacology
SN - 0021-5198
IS - 3
ER -