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A Ca 2+ ‐permeable non‐selective cation channel activated by depletion of internal Ca 2+ stores in single rabbit portal vein myocytes
Author(s) -
Albert A. P.,
Large W. A.
Publication year - 2002
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2001.013101
Subject(s) - chemistry , conductance , biophysics , cyclopiazonic acid , bapta , calmodulin , intracellular , myocyte , reversal potential , calcium , patch clamp , biochemistry , biology , receptor , microbiology and biotechnology , physics , organic chemistry , condensed matter physics
In vascular smooth muscle cells many agonists cause the release of Ca 2+ 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 Ca 2+ ‐permeable non‐selective cation channel current that is activated in rabbit portal vein myocytes by depletion of internal Ca 2+ stores. Application of cyclopiazonic acid (CPA), which depletes internal Ca 2+ stores, activated whole‐cell currents that had a reversal potential ( E r ) of about +50 mV in 1.5 m m external Ca 2+ (Ca 2 o + ). In 0 m m Ca 2 o + , the currents were larger and E r was ∼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 m m Ca 2 o + was 7 and 1.5 pS, respectively, and E r values indicated that these non‐selective cation channels are highly permeable to Ca 2+ ions. Bath application of the cell‐permeant Ca 2+ chelator, BAPTA‐AM, also activated similar currents, indicating that these channels are not activated by Ca 2+ . Spontaneous channel currents with similar properties to store‐operated channels were observed in some patches. Application of W‐7, an inhibitor of the Ca 2+ ‐binding protein calmodulin, also activated similar Ca 2+ ‐permeable channel currents. In conclusion, it is demonstrated that agents that deplete Ca 2+ stores and inhibit calmodulin binding activate Ca 2+ ‐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 Ca 2+ to refill depleted internal Ca 2+ stores and appear to possess different characteristics to store‐operated channels described in other vascular smooth muscle preparations.