Functional characterization of a Ca2+‐activated non‐selective cation channel in human atrial cardiomyocytes

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 (Iti). Iti 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 Kd 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.