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Protein Kinase C‐Dependent Inhibition of K + Currents in Noradrenaline‐Induced Depolarization of Smooth Muscle of Guinea‐Pig vas Deferens
Author(s) -
Kamimura Noritaka,
Suga Sechiko,
Nakano Kyoko,
Kanno Takahiro,
Takeo Teruko,
Wakui Makoto
Publication year - 2000
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1111/j.1469-445x.2000.01874.x
Subject(s) - depolarization , vas deferens , protein kinase c , activator (genetics) , membrane potential , biophysics , medicine , endocrinology , chemistry , guinea pig , nifedipine , protein kinase a , biology , signal transduction , kinase , biochemistry , calcium , receptor
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 α 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 μm). NA, through α 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 GDPβS, 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 α 1 ‐adrenoceptors and the subsequent activation of PKC led to inhibition of K + currents, which is responsible for the depolarization induced by NA.