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+ (K(ATP)) 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 muM) inhibited K(ATP) currents by 60.7%. Guanosine 5'-O-(2-thiodiphosphate) in the pipette (internal) solution prevented the CCh-induced inhibition of K(ATP) currents. Activators of protein kinase C (PKC), a diacylglycerol analogue, and phorbol 12-myristate 13-acetate inhibited K(ATP) currents by 63.5 and 73.9%, respectively. Blockers of PKC (bisindolylmaleimide GF-109203X and calphostin C) greatly reduced CCh inhibition of K(ATP) currents. We propose that muscarinic receptor stimulation inhibits K(ATP) channels in smooth muscle cells from urinary bladder through activation of PKC.