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Receptor‐Operated Ca 2+ ‐Permeable Nonselective Cation Channels in Vascular Smooth Muscle: A Physiologic Perspective
Author(s) -
LARGE WILLIAM A.
Publication year - 2002
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1046/j.1540-8167.2002.00493.x
Subject(s) - vascular smooth muscle , phospholipase c , medicine , biophysics , angiotensin ii , myocyte , ion channel , endocrinology , receptor , norepinephrine , transient receptor potential channel , trpc , trpc1 , chemistry , biology , smooth muscle , dopamine
Nonselective Cation Channels in Vascular Myocytes. This article summarizes the literature on receptor‐operated Ca 2+ ‐permeable nonselective cation channels in vascular smooth muscle cells. One of these conductances, the P2X 1 receptor, is a classic ligand‐gated channel, but others are likely to be mediated via G‐protein‐coupled receptors. The most studied receptor‐operated channel in vascular myocytes is the norepinephrine‐evoked nonselective cation channel in rabbit portal vein myocytes. The data regarding the transduction mechanisms and biophysical properties of whole‐cell and single‐channel currents in this preparation are described. The channels have a conductance of 20 to 25 pS and complex kinetic behavior with at least two open and two closed states. These channels are activated by norepinephrine and acetylcholine via G‐protein‐coupled receptors linked to phospholipase C and by diacylglycerol (DAG). The action of DAG occurs by a mechanism independent of protein kinase C, but other kinases may mediate the responses to norepinephrine and DAG. In addition, activation of tyrosine kinases leads to opening of this channel. Other vasoconstrictors, such as endothelin, vasopressin, serotonin, and angiotensin II, open Ca 2+ ‐permeable nonselective cation channels, but there may be differences between these conductances and the norepinephrine‐evoked channels. A homologue of the transient receptor potential protein (TRPC6) is an essential component of the norepinephrine‐activated channel in rabbit portal vein, and it is likely that this family of proteins plays an important role in mediating Ca 2+ influx in vascular smooth muscle.