The role of K^† conductances in regulating membrane excitability in human gastric corpus smooth muscle

Changes in resting membrane potential (RMP) regulate membrane excitability. K⁺ conductance(s) are one of the main factors in regulating RMP. The functional role of K⁺ conductances has not been studied the in human gastric corpus smooth muscles (HGCS). To examine the role of K⁺ channels in regulation of RMP in HGCS we employed microelectrode recordings, patch-clamp, and molecular approaches. Tetraethylammonium and charybdotoxin did not affect the RMP, suggesting that BK channels are not involved in regulating RMP. Apamin, a selective small conductance Ca2⁺-activated K⁺ channel (SK) blocker, did not show a significant effect on the membrane excitability. 4-Aminopyridine, a Kv channel blocker, caused depolarization and increased the duration of slow wave potentials. 4-Aminopyridine also inhibited a delayed rectifying K⁺ current in isolated smooth muscle cells. End-product RT-PCR gel detected Kv1.2 and Kv1.5 in human gastric corpus muscles. Glibenclamide, an ATPsensitive K⁺ channel (KATP) blocker, did not induce depolarization, but nicorandil, a KATP opener, hyperpolarized HGCS, suggesting that KATP are expressed but not basally activated. Kir6.2 transcript, a pore-forming subunit of KATP was expressed in HGCS. A low concentration of Ba2⁺, a Kir blocker, induced strong depolarization. Interestingly, Ba2⁺-sensitive currents were minimally expressed in isolated smooth muscle cells under whole-cell patch configuration. KCNJ2 (Kir2.1) transcript was expressed in HGCS. Unique K⁺ conductances regulate the RMP in HGCS. Delayed and inwardly rectifying K⁺ channels are the main candidates in regulating membrane excitability in HGCS. With the development of cell dispersion techniques of interstitial cells, the cell-specific functional significance will require further analysis.