Evolution towards higher unitary conductance in mammals makes BK channels more efficient and precise.

The large-conductance calcium-activated potassium (BK) channel plays a critical role in neuronal excitability and spike timing precision. Mammalian BK channels are distinguished by an exceptionally high unitary conductance (~250 pS), while invertebrates exhibit a significantly lower unitary conductance. We confirmed the evolutionary trend to high unitary conductance and used computational models to examine how differences in unitary conductance affect calcium activation of BK channels and influence neuronal dynamics. We show that mammalian BK channels are activated more efficiently by calcium and generate stronger repolarizing currents than lower unitary conductance channels. Channels with lower unitary conductance require greater channel density in the cell membrane, leading to stronger competition for calcium and reduced activation. In contrast, high unitary conductance channels minimize competition, enabling more effective activation and repolarization. Incorporating these channel properties into a neuronal model revealed that mammalian-type BK channels enhance spike-timing precision, consistent with the evolution of fine motor control and advanced neuronal processing in mammals.