ATP-sensitive K+ channels maintain resting membrane potential in interstitial cells of Cajal from the mouse colon

JS Na, C Hong, MW Kim, CG Park, HG Kang… - European Journal of …, 2017 - Elsevier
JS Na, C Hong, MW Kim, CG Park, HG Kang, MJ Wu, HY Jiao, S Choi, JY Jun
European Journal of Pharmacology, 2017Elsevier
To investigate the role of ATP-sensitive K+(K ATP) channels on pacemaker activity in
interstitial cells of Cajal (ICC), whole-cell patch clamping, RT-PCR, and intracellular Ca
2+([Ca 2+] i) imaging were performed in cultured colonic ICC. Pinacidil (a K+ channel
opener) hyperpolarized the membrane and inhibited the generation of pacemaker potential,
and this effect was reversed by glibenclamide (a K ATP channel blocker). RT-PCR showed
that K ir 6.1 and SUR2B were expressed in Ano-1 positive colonic ICC. Glibenclamide …
Abstract
To investigate the role of ATP-sensitive K+(KATP) channels on pacemaker activity in interstitial cells of Cajal (ICC), whole-cell patch clamping, RT-PCR, and intracellular Ca2+([Ca2+]i) imaging were performed in cultured colonic ICC. Pinacidil (a K+ channel opener) hyperpolarized the membrane and inhibited the generation of pacemaker potential, and this effect was reversed by glibenclamide (a KATP channel blocker). RT-PCR showed that Kir 6.1 and SUR2B were expressed in Ano-1 positive colonic ICC. Glibenclamide depolarized the membrane and increased pacemaker potential frequency. However, 5-hydroxydecanoic acid (a mitochondrial KATP channel blocker) had no effects on pacemaker potentials. Phorbol 12-myristate 13-acetate (PMA; a protein kinase C activator) blocked the pinacidil-induced effects, and PMA alone depolarized the membrane and increased pacemaker potential frequency. Cell-permeable 8-bromo-cyclic AMP also increased pacemaker potential frequency. Recordings of spontaneous intracellular Ca2+([Ca2+]i) oscillations showed that glibenclamide increased the frequency of [Ca2+]i oscillations. In small intestinal ICC, glibenclamide alone did not alter the generation of pacemaker potentials, and Kir 6.2 and SUR2B were expressed in Ano-1 positive ICC. Therefore, KATP channels in colonic ICC are activated in resting state and play an important role in maintaining resting membrane potential.
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