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

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Guinamard, Romain | Chatelier, Aurélien | Demion, Marie | Potreau, Daniel | Patri, Sylvie | Rahmati, Mohammad | Bois, Patrick

Edité par CCSD ; Wiley -

International audience. 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]‐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 (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 Ca²⁺ ions. The channel's open probability was increased by depolarization and a rise in internal calcium, for which the K_d 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 NSC_Ca 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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