Effects of modulators of AMP-activated protein kinase on TASK-1/3 and intracellular Ca2+ concentration in rat carotid body glomus cells

Abstract

Acute hypoxia depolarizes carotid body chemoreceptor (glomus) cells and elevates intracellular Ca2(+) concentration ([Ca2+]). Recent studies suggest that AMP-activated protein kinase (AMPK) mediates these effects of hypoxia by inhibiting the background K+ channels such as TASK. Here we studied the effects of modulators of AMPK on TASK activity in cell-attached patches. Activators of AMPK (1 mM AICAR and 0.1-0.5 mM A769662) did not inhibit TASK activity or cause depolarization during acute (10 min) or prolonged (2-3 h) exposure. Hypoxia inhibited TASK activity by similar to 70% in cells pretreated with AICAR or A769662. Both AICAR and A769662 (15-40 min) failed to increase [Ca2+, in glomus cells. Compound C (40 mu M), an inhibitor of AMPK, showed no effect on hypoxia-induced inhibition of TASK. AICAR and A769662 phosphorylatedAMPK alpha in PC12 cells, and Compound C blocked the phosphorylation. Our results suggest that AMPK does not affect TASK activity and is not involved in hypoxia-induced elevation of intracellular [Ca2+] in isolated rat carotid body glomus cells. (C) 2014 Elsevier B.V. All rights reserved.