Muscarinic receptors inhibit ATP-sensitive K+ channels in swine tracheal smooth muscle.
The patch-clamp technique was used to characterize a cromakalim-induced current and its regulation by muscarinic receptors in tracheal smooth muscle cells. Cromakalim (10 microM) activated a steady-state increase of 33-292 pA (91.2 +/- 8.8 pA, n = 43) in whole cell current, consistent with the activation of ATP-sensitive K+ (KATP) channels. Acetylcholine (10 nM-1 microM), added cumulatively, inhibited the cromakalim-induced current by 23.6 +/- 14.9 to 73.9 +/- 4.6%. This inhibition was blocked by pretreatment with atropine (1 microM). The cromakalim-induced current was also inhibited 83.0 +/- 8.3% by phorbol 12-myristate 13-acetate (100 nM, n = 6). The inhibition of the cromakalim-induced current by acetylcholine (1 microM) and phorbol 12-myristate 13-acetate (100 nM) was reduced to 27.3 +/- 3.1% (n = 10) and 32.8 +/- 7.8% (n = 3), respectively, in the presence of staurosporine (100 microM). We conclude that muscarinic receptor stimulation inhibits KATP channel activity through the activation of protein kinase C. These findings suggest that KATP channels may play a role in the regulation of membrane potential and contractility in airway smooth muscle.
Nuttle
L C
LC
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216, USA.
Farley
J M
JM
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D019806:Cromakalim; D004553:Electric Conductivity; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D011758:Pyrroles / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000502:physiology*; D013552:Swine; D014132:Trachea / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology
D001578:Benzopyrans; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011758:Pyrroles; D011976:Receptors, Muscarinic; D019806:Cromakalim; D000255:Adenosine Triphosphate; D011493:Protein Kinase C