Dual modulation of an inwardly rectifying potassium conductance.
The modulation of a constitutively active IRK1-like inwardly rectifying potassium channel, that is endogenously expressed in the RBL-2H3 cell, was studied with the whole-cell patch-clamp technique. Activation of G-proteins by intracellular application of GTP gamma S revealed a dual modulation of the inward rectifier. An initial increase in inward current amplitude was induced by GTP gamma S, followed by a profound inhibition of the current. The stimulation of the inward rectifier by GTP gamma S was abolished by pretreatment with pertussis toxin. The inhibitory phase of the GTP gamma S-induced response was pertussis toxin-insensitive. Stimulation of the m1-muscarinic receptor expressed in the RBL cell after stable transfection, induced an inhibition of the inwardly rectifying currents. Application of protein kinase C activators such as phorbol 12-myristate 13-acetate and phorbol 12,13-dibutyrate, resulted in a strong inhibition of the currents. Application of the cAMP-dependent protein kinase activator 8-bromo cAMP also induced an inhibition of the inward rectifier. It is concluded that the inward rectifier of the RBL-2H3 cell may be inhibited both by activation of protein kinase C and by cAMP-dependent protein kinase. As this type of inward rectifier is widely expressed in the nervous system, these data imply that the channel can be inhibited by receptors that stimulate phospholipase C and/or stimulate adenylyl cyclase, and can be activated by receptors that inhibit adenylyl cyclase activity.
Jones
S V
SV
Department of Psychiatry, University of Vermont College of Medicine, Burlington 05405, USA.
D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004594:Electrophysiology; D004789:Enzyme Activation / Q000187:drug effects; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology*; D015471:Leukemia, Basophilic, Acute / Q000473:pathology; D008564:Membrane Potentials / Q000502:physiology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011976:Receptors, Muscarinic / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D014982:Xenopus laevis
D018721:Muscarinic Agonists; D015221:Potassium Channels; D011976:Receptors, Muscarinic; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C