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.
- Ca2+ channels
- Intracellular calcium concentration
- K+ channels
- Thromboxane A2 analogue
ASJC Scopus subject areas