Calcitonin gene-related peptide activates the K+ channels of vascular smooth muscle cells via adenylate cyclase.
The aim of the present study was to examine the effects of calcitonin gene-related peptide (CGRP) on the K+ channels of vascular smooth muscle cells. Cultured smooth muscle cells from a porcine coronary artery were studied using the patch-clamp technique. Extracellular application of 100 nM CGRP activated two types of K+ channels, the Ca(2+)-activated K+ channel (KCa channel) and the ATP-sensitive K+ channel (KATP channel) in cell-attached patch configurations. In cells pretreated with Rp-cAMPS, a membrane-permeable inhibitor of cAMP-dependent protein kinase (PKA), extracellular application of 100 nM CGRP could not activate the KCa or KATP channel, indicating that the activation of the K+ channels by CGRP occurs in connection with PKA. In the cell-attached patch configurations, extracellular application of 1 mM dibutyryl cAMP, a membrane permeable cAMP, activated KCa and KATP channels. In inside-out patch configurations, application of PKA to the cytosolic side activated both the KCa and KATP channels. These results indicate that CGRP modulates the K+ channels of vascular smooth muscle cells via adenylate cyclase, i.e., cAMP-PKA pathway, and contributes to control of vascular tone.
Miyoshi
H
H
Department of Nutrition School of Medicine, University of Tokushima, Japan.
Nakaya
Y
Y
D000262:Adenylyl Cyclases / Q000502:physiology*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D000242:Cyclic AMP / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D013552:Swine
D015221:Potassium Channels; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015740:Calcitonin Gene-Related Peptide