Functional characterization of a Ca2+-activated non-selective cation channel in human atrial cardiomyocytes |
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Authors: | Romain Guinamard Aurélien Chatelier Marie Demion Daniel Potreau Sylvie Patri Mohammad Rahmati Patrick Bois |
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Institution: | Institut de Physiologie et Biologie Cellulaires, CNRS UMR 6187, Universitéde Poitiers, 86022 Poitiers Cedex, France |
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Abstract: | Cardiac arrhythmias, which occur in a wide variety of conditions where intracellular calcium is increased, have been attributed to the activation of a transient inward current ( I ti). I ti is the result of three different Ca]i-sensitive currents: the Na+–Ca2+ exchange current, a Ca2+-activated chloride current and a Ca2+-activated non-selective cationic current. Using the cell-free configuration of the patch-clamp technique, we have characterized the properties of a Ca2+-activated non-selective cation channel (NSCCa) in freshly dissociated human atrial cardiomyocytes. In excised inside-out patches, the channel presented a linear I–V relationship with a conductance of 19 ± 0.4 pS. It discriminated poorly among monovalent cations (Na+ and K+) and was slightly permeable to Ca2+ ions. The channel's open probability was increased by depolarization and a rise in internal calcium, for which the K d for Ca2+]i was 20.8 μ m . Channel activity was reduced in the presence of 0.5 m m ATP or 10 μ m glibenclamide on the cytoplasmic side to 22.1 ± 16.8 and 28.5 ± 8.6%, respectively, of control. It was also inhibited by 0.1 m m flufenamic acid. The channel shares several properties with TRPM4b and TRPM5, two members of the 'TRP melastatin' subfamily. In conclusion, the NSCCa channel is a serious candidate to support the delayed after-depolarizations observed in Ca2+] overload and thus may be implicated in the genesis of arrhythmias. |
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