A Ca2+-permeable non-selective cation channel activated by depletion of internal Ca2+ stores in single rabbit portal vein myocytes

A. P. Albert, W. A. Large

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Abstract

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 (Er) of about +50 mV in 1.5 mM external Ca2 (CaO2+). In 0 mM CaO2+, the currents were larger and Er 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 Er of +20 mV. The slope conductance in 0 and 110 mm CaO2+ was 7 and 1.5 pS, respectively, and Er 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.

Original languageEnglish
Pages (from-to)717-728
Number of pages12
JournalJournal of Physiology
Volume538
Issue number3
DOIs
Publication statusPublished - 1 Feb 2002

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