Abstract
An inwardly rectifying K + current, which was heterologously expressed in Xenopus oocytes, was inhibited by isoproterenol, a β-adrenergic agonist. Poly(A) + mRNA isolated from guinea-pig brain was injected into oocytes 2–3 days before experiments. Isoproterenol inhibition of the K + current was time- and voltage-dependent: the inhibition became faster and more pronounced as the command voltage steps were applied to more negative potentials. This inhibition was prevented by propranolol. Dibutylyl cyclic (dB-c) AMP could mimic the effect of isoproterenol, while injection of the catalytic subunit of cAMP-dependent protein kinase into the oocytes did not affect the K + current. Inhibitors of the protein kinases, WIPTIDE and H-8, did not prevent the inhibition by dB-cAMP. Furthermore, dB-cGMP also inhibited the K + current in a similar time- and voltage-dependent manner. We propose that the phosphorylation-independent action of cyclic nucleotides mediates β-adrenergic inhibition of brain inwardly rectifying K + channels expressed in Xenopus oocytes.
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