Receptor-operated Ca2(+)-permeable nonselective cation channels in vascular smooth muscle: a physiologic perspective.
This article summarizes the literature on receptor-operated Ca2(+)-permeable nonselective cation channels in vascular smooth muscle cells. One of these conductances, the P2X1 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 Ca2(+)-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 Ca2+ influx in vascular smooth muscle.
Large
William A
WA
Department of Pharmacology and Clinical Pharmacology, St. George's Hospital Medical School, London, United Kingdom. w.large@sghms.ac.uk
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D004075:Diglycerides / Q000494:pharmacology; D004553:Electric Conductivity; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000502:physiology; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology; D058469:Receptors, Purinergic P2X; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D015220:Calcium Channels; D004075:Diglycerides; D007473:Ion Channels; D011941:Receptors, Adrenergic; D011956:Receptors, Cell Surface; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D015222:Sodium Channels; D014662:Vasoconstrictor Agents; D002118:Calcium