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 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.
Hatakeyama
N
N
Program in Smooth Muscle Research, Harvard-Thorndike Lab, Boston, Massachusetts, USA.
Wang
Q
Q
Goyal
R K
RK
Akbarali
H I
HI
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D004947:Esophagus / Q000166:cytology / Q000378:metabolism*; D009116:Muscarine / Q000378:metabolism*; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects; D011493:Protein Kinase C / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000145:classification / Q000502:physiology
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011976:Receptors, Muscarinic; D009116:Muscarine; D000255:Adenosine Triphosphate; D002217:Carbachol; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D002118:Calcium