Calcium-activated potassium channels are selectively coupled to P/Q-type calcium channels in cerebellar Purkinje neurons.
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.
Womack
Mary D
MD
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Chevez
Carolyn
C
Khodakhah
Kamran
K
D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020865:Calcium Channels, P-Type / Q000378:metabolism / Q000502:physiology*; D020907:Calcium Channels, Q-Type / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D017136:Ion Transport; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism*; D011689:Purkinje Cells / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D024681:Potassium Channels, Calcium-Activated; D002118:Calcium