Protein kinase C-dependent inhibition of K+ currents in noradrenaline-induced depolarization of smooth muscle of guinea-pig vas deferens

Ionic mechanisms and signal transduction underlying noradrenaline (NA)-indu ced depolarization in single smooth muscle cells of guinea-pig vas deferens were studied. NA caused depolarization followed by action potentials throu gh activation of alpha(1)-adrenoceptors, In the presence of nifedipine, no action potential was generated, and the magnitude of the depolarization dep ended on the concentration of NE (0.1-100 mu M). NA, through alpha(1)-adren oceptor activation, reduced the magnitude of membrane currents in response to voltage ramp pulses from -90 to -30 mV in a concentration-dependent mann er. The reversal potential of the current inhibited by NA changed proportio nally to the change in the equilibrium potential of K+, suggesting that NA inhibited K+ channel activity Treatment of cells with GDP beta S, an inhibi tor of G proteins, or bisindolylmaleimide (BIM), a selective protein kinase C (PKC) inhibitor, prevented the NA inhibition of the currents. Applicatio n of 12-O-tetradecanoylphorbol 13-acetate (TPA), an activator of PKC, mimic ked the effect of NE. It is suggested that in the smooth muscle of guinea-p ig vas deferens, activation of alpha(1)-adrenoceptors and the subsequent ac tivation of PKC led to inhibition of K+ currents, which is responsible for the depolarization induced by NA.