Aims: 

Temporal synchrony between cardiac action potential (AP) and Ca²⁺ cycle may directly or indirectly (via signalling pathways) facilitate Ca²⁺-dependent modulation of ion channels resulting in alterations in the shape and duration of the AP. Putative control of Ca²⁺_i on the repolarization may have pivotal significance, since repolarization abnormalities often lead to severe cardiac arrhytmias. We aimed to determine the significance of the small conductance Ca²⁺-activated (SK) channels, to test the [Ca²⁺]_i sensitivity of the inward rectifier potassium current (I_K1), and to analyze the possible role of these currents in repolarization.

Results: 

We found that SK channel-like proteins are, indeed, expressed in both canine and rat cardiomyocytes, however, could not demonstrate significant SK current and concludedthat these channels are probably not physiologically functional. In contrast, the elevation of external [Ca²⁺] from 2 mM to 4 mM caused significant acceleration of the terminal phase of repolarization. Furthermore, the effect of selective I_K1 inhibition (10 mM BaCl₂)was largely enchanced in the presence of elevated [Ca²⁺]_i. These results were directly verified in voltage-clamp measurements: the magnitude of I_K1 (the Ba²⁺-sensitive current) was greatly increased with elevated [Ca²⁺]_i (900 nM) as compared to the low (160 nM) [Ca²⁺]_i setting.

Conclusions: 

The repolarization phase of the AP is to some extent under the control of Ca²⁺_i.This control, however, is not established via SK current but via the activation of I_K1. The [Ca²⁺]_i-control of repolarization may facilitate frequency-adaptation, and may serve as an endogenous protective mechanism, decreasing the probability of [Ca²⁺]_i-induced arrhytmias.