[Ca²⁺] overload leads to cardiac arrhythmias induced by delayed afterdepolarisations, and has been attributed to a transient inward current (I_ti). This current appears to be the result of Na²⁺-Ca²⁺ exchange, a Ca²⁺-activated chloride current and a Ca²⁺-activated non-selective cationic current (Ehara et al. 1988). Using the cell-free configuration of the patch-clamp technique, we have characterized the electrophysiological properties of a Ca²⁺-activated non-selective cation channel (NSC_Ca) on freshly dissociated human atrial cardiomyocytes.

Myocardium specimens were obtained from patients undergoing cardiac surgery according to the European Community Council Directive. All patients had normal sinusal rhythmicity. Cells were obtained by both enzymatic and mechanical dissociation. Before patching, cells were incubated for at least 10 min with 500 nM phorbol 12-myristate, 13-acetate (PMA), a PKC activator. Channel currents were recorded in inside-out patches bathed on both sides with a solution containing (mM): 140 NaCl, 4.8 KCl, 1.2 MgCl₂, 1 CaCl₂, 10 glucose and 10 Hepes. In these conditions, the channel had a linear current-voltage relationship (λ = 19 ± 0.4 pS, mean ± S.E.M., n = 7). Depolarisation increased channel open probability. Ion substitution experiments indicated that the channel discriminated poorly among monovalent cations (P_K/P_Na = 1.17 ± 0.08, n = 6), and was impermeable to Cl^– (P_Cl/P_Na = 0.1 ± 0.04, n = 6) and Ca²⁺ (P_Ca/P_Na = 0.13 ± 0.03, n = 3). Possible regulatory properties of the channel were investigated; channel openings were seen at 1 mM [Ca²⁺]_i but not at 1 nM (n = 6). The channel activity was reduced to about 50 % of the control (n = 3) by the intracellular application of 1 mM ATP.

As a rise in [Ca²⁺] increases channel activity, we conclude that the NSC_Ca channel is a good candidate to support, at least in part, delayed afterdepolarisations observed in [Ca²⁺] overload and thus could be implicated in arrhythmia generation. Interestingly, we previously showed that a similar channel was present on dedifferentiated rat cardiomyocytes in culture, a model of cardiac hypertrophy that leads to arrhythmia (Guinamard et al. 2002).

All procedures accord with the Declaration of Helsinki.