A Ca2+-permeable non-selective cation channel activated by depletion of internal Ca2+ stores in single rabbit portal vein myocytes.
In vascular smooth muscle cells many agonists cause the release of Ca2+ ions from internal stores. An important problem concerns the mechanism by which the intracellular stores are refilled subsequent to depletion. In the present study, we describe the properties of a Ca2+-permeable non-selective cation channel current that is activated in rabbit portal vein myocytes by depletion of internal Ca2+ stores. Application of cyclopiazonic acid (CPA), which depletes internal Ca2+ stores, activated whole-cell currents that had a reversal potential (E(r)) of about +50 mV in 1.5 mM external Ca2+ (Ca2+o). In 0 mM Ca2+o, the currents were larger and E(r) was approximately 0 mV. Application of CPA and caffeine during cell-attached recording activated single inward channel currents at negative potentials, which had a slope conductance of 2-3 pS and an E(r) of +20 mV. The slope conductance in 0 and 110 mM Ca2+o was 7 and 1.5 pS, respectively, and E(r) values indicated that these non-selective cation channels are highly permeable to Ca2+ ions. Bath application of the cell-permeant Ca2+ chelator, BAPTA-AM, also activated similar currents, indicating that these channels are not activated by Ca2+. Spontaneous channel currents with similar properties to store-operated channels were observed in some patches. Application of W-7, an inhibitor of the Ca2+-binding protein calmodulin, also activated similar Ca2+-permeable channel currents. In conclusion, it is demonstrated that agents that deplete Ca2+ stores and inhibit calmodulin binding activate Ca2+-permeable non-selective cation channel currents in rabbit portal vein myocytes. These channels may have an important role in vascular smooth muscle in providing an influx of Ca2+ to refill depleted internal Ca2+ stores and appear to possess different characteristics to store-operated channels described in other vascular smooth muscle preparations.
Albert
A P
AP
Department of Pharmacology and Clinical Pharmacology, St George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, UK.
Large
W A
WA
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002412:Cations / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D007477:Ions; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010539:Permeability; D011169:Portal Vein / Q000166:cytology / Q000378:metabolism*; D011817:Rabbits; D013449:Sulfonamides / Q000494:pharmacology
D002147:Calmodulin; D002412:Cations; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D007211:Indoles; D007473:Ion Channels; D007477:Ions; D013449:Sulfonamides; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D002110:Caffeine; D004533:Egtazic Acid; C017967:W 7; D002118:Calcium; C000543:cyclopiazonic acid