Large conductance Ca²⁺ and voltage-activated potassium channels (BK_Ca) shape the spiking in many types of excitable cell through their re/hyperpolarizing K⁺ conductance. Onset and duration of the BK_Ca-mediated currents appear cell-type specific and vary between one and a few ten milliseconds. Reliable activation of BK_Ca channels under cellular conditions is enabled by their integration into complexes with voltage-activated Ca²⁺ (Cav) channels that provide Ca²⁺ ions at concentrations sufficiently high (= 10 mM) for activation of BK_Ca in the physiological voltage-range. Formation of BK_Ca-Cav complexes is restricted to a subset of Cav channels, Cav1.2 (L-type), Cav2.1 (P/Q-type) and Cav2.2 (N-type) with distinct expression pattern and gating properties.

Electrophysiological experiments with heterologously reconstituted ion channels revealed distinct functional properties of channel complexes composed of BK_Ca and either Cav1.2 or Cav2.1. Under steady-state conditions, K⁺ currents mediated by BK_Ca-Cav2.1 complexes exhibit a considerably faster rise time and reach maximum at potentials more negative than complexes formed by BK_Ca and Cav1.2, in line with the distinct gating kinetics of the two Cav subunits. When AP waveforms were used as a command, hyperpolarizations by BK_Ca-Cav2.1 occurred at shorter APs and lasted longer than that of BK_Ca-Cav1.2. These results demonstrate that the repolarizing K⁺ currents through BK_Ca-Cav complexes are controlled by the Cav subunit and may thus be adapted to the particular requirements of distinct types of cell.