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

Albert, A. P. ORCID: https://orcid.org/0000-0002-3596-9634 and Large, W. A. (2002) A Ca2+-permeable non-selective cation channel activated by depletion of internal Ca2+ stores in single rabbit portal vein myocytes. Journal of Physiology, 538 (3). pp. 717-728. ISSN 0022-3751

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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.

Item Type: Article
Uncontrolled Keywords: physiology ,/dk/atira/pure/subjectarea/asjc/1300/1314
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 29 Oct 2024 09:30
Last Modified: 03 Nov 2024 07:31
URI: https://ueaeprints.uea.ac.uk/id/eprint/97281
DOI: 10.1113/jphysiol.2001.013101

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