Muscarinic inhibition of ATP-sensitive K+ channels by protein kinase C in urinary bladder smooth muscle.

Access to files

Full-text and supplementary files are not available from Manchester eScholar. Use our list of Related resources to find this item elsewhere. Alternatively, request a copy from the Library's Document supply service.

Abstract

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.

Keyword(s)

Animals; Cromakalim; Guinea Pigs; Muscarinic Antagonists; analogs & derivatives: Guanosine Diphosphate; antagonists & inhibitors: Protein Kinase C; drug effects: Membrane Potentials; drug effects: Muscle, Smooth; drug effects: Potassium Channels; drug effects: Receptors, Muscarinic; drug effects: Urinary Bladder; pharmacology: Adenosine Triphosphate; pharmacology: Benzopyrans; pharmacology: Carbachol; pharmacology: Diglycerides; pharmacology: Glyburide; pharmacology: Indoles; pharmacology: Maleimides; pharmacology: Pyrroles; pharmacology: Tetradecanoylphorbol Acetate; pharmacology: Thionucleotides

Bibliographic metadata

Institutional metadata

Record metadata