Muscarinic inhibition of ATP-sensitive K+ channels by protein kinase C in urinary bladder smooth muscle.
We explored the possibility that muscarinic receptor stimulation can inhibit ATP-sensitive K+ (KATP) channels in smooth muscle cells from guinea pig urinary bladder. Whole cell K+ currents were measured in smooth muscle cells isolated from the detrusor muscle of the guinea pig bladder. Stimulation of muscarinic receptors by carbachol (CCh; 10 microM) inhibited KATP currents by 60.7%. Guanosine 5'-O-(2-thiodiphosphate) in the pipette (internal) solution prevented the CCh-induced inhibition of KATP currents. Activators of protein kinase C (PKC), a diacylglycerol analogue, and phorbol 12-myristate 13-acetate inhibited KATP currents by 63.5 and 73.9%, respectively. Blockers of PKC (bisindolylmaleimide GF-109203X and calphostin C) greatly reduced CCh inhibition of KATP currents. We propose that muscarinic receptor stimulation inhibits KATP channels in smooth muscle cells from urinary bladder through activation of PKC.
Bonev
A D
AD
Department of Pharmacology, University of Vermont, Colchester 05446-2500.
Nelson
M T
MT
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D019806:Cromakalim; D004075:Diglycerides / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D018727:Muscarinic Antagonists; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*
D001578:Benzopyrans; D004075:Diglycerides; D007211:Indoles; D008301:Maleimides; D018727:Muscarinic Antagonists; D015221:Potassium Channels; D011758:Pyrroles; D011976:Receptors, Muscarinic; D013873:Thionucleotides; D019806:Cromakalim; D006153:Guanosine Diphosphate; C023427:guanosine 5'-O-(2-thiodiphosphate); C038237:1-oleoyl-2-acetylglycerol; D000255:Adenosine Triphosphate; D002217:Carbachol; D011493:Protein Kinase C; C070515:bisindolylmaleimide I; D013755:Tetradecanoylphorbol Acetate; D005905:Glyburide