Effects of modulators of AMPK on TASK K+ channel and [Ca2+] in rat carotid body glomus cells

Abstract

Acute hypoxia depolarizes and elevates intracellular Ca2+ concentration ([Ca2+]i) in carotid body glomus cells. Recent studies suggest that AMP‐activated protein kinase (AMPK) mediates these effects of hypoxia by inhibiting background K+ channels such as TASK. To obtain additional evidence for the role of AMPK, we studied the effect of modulators of AMPK on TASK activity in cell‐attached patches of rat glomus cells. Perfusion of glomus cells for ~10 min with AICAR (1 mM) and A769662 (0.1 mM), two activators of AMPK, did not inhibit TASK activity or elicit depolarization. When cells were incubated with AICAR (1 mM), A769662 (0.1 mM), or DMSO (0.1%) for 2–3 hr, TASK activities in the three groups were also not significantly different. Furthermore, hypoxia inhibited TASK activity by 72% and 75% in cells pretreated with AICAR or A769662, respectively. Both AICAR and A769662 failed to increase [Ca2+]i in glomus cells. Compound C (40 μM) did not prevent hypoxia‐induced inhibition of TASK. AICAR and A769662 phosphorylated AMPKα in PC12 cells, and this was prevented by Compound C. Together, these findings suggest that inhibition of TASK by hypoxia is not mediated by AMPK. (supported by NIH and AHA)