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)-induced depolarization in single smooth muscle cells of guinea-pig vas deferens were studied. NA caused depolarization followed by action potentials through activation of 1-adrenoceptors. In the presence of nifedipine, no action potential was generated, and the magnitude of the depolarization depended on the concentration of NA (0.1-100 micrometer). NA, through 1-adrenoceptor activation, reduced the magnitude of membrane currents in response to voltage ramp pulses from -90 to -30 mV in a concentration-dependent manner. The reversal potential of the current inhibited by NA changed proportionally to the change in the equilibrium potential of K+, suggesting that NA inhibited K+ channel activity. Treatment of cells with GDPS, an inhibitor of G proteins, or bisindolylmaleimide (BIM), a selective protein kinase C (PKC) inhibitor, prevented the NA inhibition of the currents. Application of 12-O-tetradecanoylphorbol 13-acetate (TPA), an activator of PKC, mimicked the effect of NA. It is suggested that in the smooth muscle of guinea-pig vas deferens, activation of 1-adrenoceptors and the subsequent activation of PKC led to inhibition of K+ currents, which is responsible for the depolarization induced by NA.
Kamimura
N
N
Department of Physiology, Hirosaki University School of Medicine, Hirosaki 036-8562, Japan.
Suga
S
S
Nakano
K
K
Kanno
T
T
Takeo
T
T
Wakui
M
M
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002469:Cell Separation; D004594:Electrophysiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D011493:Protein Kinase C / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D014649:Vas Deferens / Q000166:cytology / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D026902:Potassium Channel Blockers; D011493:Protein Kinase C; D009638:Norepinephrine