Phosphorylation-independent inhibition by intracellular cyclic nucleotides of brain inwardly rectifying K+ current expressed in Xenopus oocytes.
An inwardly rectifying K+ current, which was heterologously expressed in Xenopus oocytes, was inhibited by isoproterenol, a fadrenergic 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 beta-adrenergic inhibition of brain inwardly rectifying K+ channels expressed in Xenopus oocytes.
Ito
H
H
Department of Cell Biology and Signaling, Yamagata University School of Medicine, Iida-nishi, Japan.
Tsuchimochi
H
H
Tada
Y
Y
Kurachi
Y
Y
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D006168:Guinea Pigs; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials; D009865:Oocytes; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D014981:Xenopus
D000318:Adrenergic beta-Agonists; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D001464:Barium; D003995:Dibutyryl Cyclic GMP; D003994:Bucladesine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D006152:Cyclic GMP; D007545:Isoproterenol