Calcitonin-gene-related peptide activates the muscarinic-gated K+ current in atrial cells.
A high density of nerve fibers containing calcitonin-gene-related peptide (CGRP) is present in the atria. Recently CGRP was reported to open ATP-sensitive K channels in arterial smooth muscle cells. This study examines whether CGRP activates a similar K+ channel in cardiac cells. In voltage-clamped whole cells loaded with GTP and ATP, CGRP reversibly evoked an inwardly rectifying K+ current. To identify the K+ channel that gives rise to this current, three types of K+ channel (resting, ATP-sensitive and acetylcholine-activated) were examined. CGRP failed to activate or inhibit the ATP-sensitive or the resting K+ channel. However, CGRP (0.1-1 microM) caused activation of single channels with kinetics similar to that of the muscarinic K+ channel (35-40 pS conductance and approx. 1 ms mean open time in symmetrical 140 mM K+). In excised, inside-out (CGRP in pipette) or in outside-out (GTP in pipette) patches, the K+ current was activated by perfusion with GTP or CGRP, respectively, suggesting that CGRP activated the muscarinic K+ channel via GTP-binding protein. Treatment with pertussis toxin inhibited the activation of the K+ channel, suggesting that CGRP receptor may be coupled to a Gi or a Go type of GTP-binding protein. Together with previous findings, these results suggest that CGRP modulates several types of ion channels to produce its cellular effects.
Kim
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Department of Physiology and Biophysics, Chicago Medical School, IL 60064.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D016275:Atrial Function; D001693:Biological Transport, Active / Q000187:drug effects / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000502:physiology; D006325:Heart Atria / Q000166:cytology* / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009116:Muscarine / Q000494:pharmacology*; D037342:Pertussis Toxin; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015221:Potassium Channels; D010566:Virulence Factors, Bordetella; D009116:Muscarine; D000255:Adenosine Triphosphate; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D015740:Calcitonin Gene-Related Peptide; D011188:Potassium