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Functional characterization of a Ca 2+ ‐activated non‐selective cation channel in human atrial cardiomyocytes
Author(s) -
Guinamard Romain,
Chatelier Aurélien,
Demion Marie,
Potreau Daniel,
Patri Sylvie,
Rahmati Mohammad,
Bois Patrick
Publication year - 2004
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.2004.063974
Subject(s) - flufenamic acid , chemistry , biophysics , depolarization , patch clamp , calcium , ion channel , glibenclamide , conductance , membrane potential , biochemistry , endocrinology , biology , receptor , mathematics , organic chemistry , combinatorics , diabetes mellitus
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 + –Ca 2+ exchange current, a Ca 2+ ‐activated chloride current and a Ca 2+ ‐activated non‐selective cationic current. Using the cell‐free configuration of the patch‐clamp technique, we have characterized the properties of a Ca 2+ ‐activated non‐selective cation channel (NSC Ca ) 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 Ca 2+ ions. The channel's open probability was increased by depolarization and a rise in internal calcium, for which the K d for [Ca 2+ ] 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 NSC Ca channel is a serious candidate to support the delayed after‐depolarizations observed in [Ca 2+ ] overload and thus may be implicated in the genesis of arrhythmias.