U46619, a thromboxane A2 agonist, inhibits KCa channel activity from pig coronary artery

Abstract

Thromboxane A2 (TxA2) is a potent vasoconstrictor derived from the metabolism of arachidonic acid. Because potassium channels are involved in the contraction of vascular smooth muscle, their blockade could contribute to the TxA2-induced contraction. To test this possibility, we studied the effect of the TxA2 stable analogue U46619 on calcium-activated potassium (KCa) channels from coronary artery reconstituted into lipid bilayers. Addition of U46619 (50-150 nM) to the external but not to the internal side of the channel decreased the channel open probability (Po) between 15 and 80% of the control value. The inhibitory effect of U46619 affected both the open and closed states of the channel and could be reversed by internal calcium. Thromboxane B2, the inactive hydrolysis derivative of TxA2, did not affect channel activity. SQ 29548, a TxA2 receptor antagonist, was able to prevent the inhibition by U46619. Furthermore, SQ 29548 added after U46619 could restore channel activity to near control values. These results suggest that TxA2 could be a regulatory factor of KCa channels from coronary smooth muscle and that this regulation could be related to its action as a vasoconstrictor.