Am J Physiol Cell Physiol AJP: Endocrinology and Metabolism
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Am J Physiol Cell Physiol 268: C877-C885, 1995;
0363-6143/95 $5.00
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AJP - Cell Physiology, Vol 268, Issue 4 C877-C885, Copyright © 1995 by American Physiological Society

ARTICLES

Muscarinic suppression of ATP-sensitive K+ channel in rabbit esophageal smooth muscle

N. Hatakeyama, Q. Wang, R. K. Goyal and H. I. Akbarali
Program in Smooth Muscle Research, Harvard-Thorndike Lab, Boston, Massachusetts, USA.

Smooth muscle cells from the rabbit esophageal muscularis mucosae were studied for the presence of ATP-sensitive K+ channel (KATP) and its inhibition by carbachol. Lemakalim (10 microM), 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 microM) completely abolished the lemakalim-induced currents. These currents were therefore denoted as KATP. Carbachol (10 microM) suppressed KATP 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 M3 receptor antagonist, p-flurohexahydrosiladifenidol (0.1 microM). KATP 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 KATP is via M3 receptor subtype and the signaling pathway involves Ca2+, protein kinase C, and tyrosine kinase.


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