P.35 TASK-1 Channels Play an Anticontractile Role in Rat Septal Coronary Artery Under Pharmacological Blockade of Endothelium

Abstract

Purpose/Background/Objectives

TASK-1 (TWIK-related acid-sensitive potassium) channels conduct background K⁺ currents in smooth muscle cells of pulmonary arteries suppressing vasocontraction. However, the vasomotor role of TASK-1 channels in systemic arteries as well as their regulation by the endothelium are poorly understood. Therefore, we investigated the impact of TASK-1 channels on the regulation of arterial contraction in the presence or absence of the relaxing influence of the endothelium in the brain and the heart, important regions of the systemic circulation.

Methods

Segments of basilar and septal coronary arteries (2-mm long) were isolated from male Wistar rats and mounted in a wire myograph. The functional impact of TASK-1 channels was assessed by the effect of their blocker AVE1231 (1 µM) on contractile responses to the thromboxane A2 receptor agonist U46619. Experiments were performed first on endothelium-intact arteries and then after combined blockade of NO-synthase (L-NNA, 100 µM), cyclooxygenase (indomethacin, 10 µM) and EDHF (TRAM34, 1 µM and UCL1684, 0.1 µM).

Results

AVE1231 did not change basal tone and contractile responses to U46619 of either basilar or septal coronary arteries with intact endothelium. However, incubation with AVE1231 after pharmacological blockade of the endothelium led to the development of basal tone and augmented contractile responses to U46619 in septal coronary arteries, but not in basilar arteries.

Conclusions

TASK-1 channels may play a protective anticontractile role in the coronary circulation under conditions of endothelial dysfunction.

Supported by RSF (grant N 20-75-00027). We thank Sanofi for the gift of AVE1231.