MUSCARINIC SUPPRESSION OF ATP-SENSITIVE K+ CHANNEL IN RABBIT ESOPHAGEAL SMOOTH-MUSCLE

Smooth muscle cells from the rabbit esophageal muscularis mucosae were studied for the presence of ATP-sensitive KS channel (K-ATP) and its inhibition by carbachol. Lemakalim (10 mu M), a synthetic K+ channel opener, increased whole cell currents by -174 +/- 15 pA with 0.1 mM intracellular ATP concentration ([ATP](i)) and -70 +/- 11 pA with 5 mM [ATP](i). Glibenclamide (10 mu M) completely abolished the lemakalim-induced currents. These currents were therefore denoted as K-ATP Carbachol (10 mu M) suppressed K-ATP by 74 +/- 4 % with 10 mM intracellular ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) concentration and 100% when EGTA was omitted from the pipette solution. Carbachol suppression was attenuated to 23 +/- 16% by the M(3) receptor antagonist, p-flurohexahydrosiladifenidol (0.1 mu M). K-ATP was also suppressed by phorbol 12-myristate 13-acetate (PMA; 100 nM) by 63 +/- 9%. The effects of both PMA and carbachol were significantly reduced by inhibitors of protein kinase C and tyrosine kinase. These results suggest that carbachol suppression of K-ATP is via Mg receptor subtype and the signaling pathway involves Ca2+, protein kinase C, and tyrosine kinase.