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

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• 作者：Donghee Kim^a ; ^{Donghee.kim@rosalindfranklin.edu" class="auth_mail} ; Dawon Kang^a ; ^b ; Elizabeth A. Martin^a ; Insook Kim^c ; John L. Carroll^c ; ^{carrolljohnl@uams.edu" class="auth_mail}
• 关键词：Hypoxia ; Carotid body ; Chemoreceptors ; AMP kinase ; Background K+ channels
• 刊名：Respiratory Physiology & Neurobiology
• 出版年：1 May, 2014
• 年：2014
• 卷：195
• 期：Complete
• 页码：19-26
• 全文大小：1280 K

文摘

Acute hypoxia depolarizes carotid body chemoreceptor (glomus) cells and elevates intracellular Ca²⁺ concentration ([Ca²⁺]_i). 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 鈭?0% in cells pretreated with AICAR or A769662. Both AICAR and A769662 (15-40 min) failed to increase [Ca²⁺]_i in glomus cells. Compound C (40 渭M), an inhibitor of AMPK, showed no effect on hypoxia-induced inhibition of TASK. AICAR and A769662 phosphorylated AMPK伪 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.