Article Dans Une Revue The Journal of Physiology Année : 2004

Functional characterization of a Ca 2+ ‐activated non‐selective cation channel in human atrial cardiomyocytes

Résumé

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 (Iti). Iti is the result of three different [Ca]‐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 IV 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 Kd for [Ca]i was 20.8 μM. Channel activity was reduced in the presence of 0.5 mM ATP or 10 μM 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 mM 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.

Dates et versions

hal-05024483 , version 1 (08-04-2025)

Identifiants

Citer

Romain Guinamard, Aurélien Chatelier, Marie Demion, Daniel Potreau, Sylvie Patri, et al.. Functional characterization of a Ca 2+ ‐activated non‐selective cation channel in human atrial cardiomyocytes. The Journal of Physiology, 2004, 558 (1), pp.75-83. ⟨10.1113/jphysiol.2004.063974⟩. ⟨hal-05024483⟩

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