Calcium-Activated Potassium Channels Are Selectively Coupled to P/Q-Type Calcium Channels in Cerebellar Purkinje Neurons

摘要

Cerebellar Purkinje neurons fire spontaneously in the absence of synaptic transmission. P/Q-type voltage-gated calcium channels and calcium-activated potassium channels are required for normal spontaneous activity. Blocking P/Q-type calcium channels paradoxically mimics the effects of blocking calcium-activated potassium channels. Thus, an important function of the P/Q-type calcium channels is to provide calcium for activation of calcium-activated potassium channels. Purkinje neurons express several classes of voltage-gated calcium channels, and the P/Q- and T-type channels make comparable contributions to total calcium entry after an action potential. Here we demonstrate that calcium-activated potassium channels are activated exclusively by calcium entering through P/Q-type voltage-gated calcium channels. This selective coupling is maintained even when calcium flux through voltage-gated channels is increased by increasing the extracellular calcium concentration. Small decreases in P/Q current density are likely to alter spontaneous activity of Purkinje neurons via decreased recruitment of calcium-activated potassium channels. In both human and murine animal models, mutations that decrease P/Q current density in Purkinje neurons also cause cerebellar ataxia. Alterations in the spontaneous activity of Purkinje neurons may be an important contributing factor to the ataxia in these subjects.