Functional Roles of an ERG Current Isolated in Cerebellar Purkinje Neurons

Abstract

Transcripts encoding ERG potassium channels are expressed by most neurons of the CNS. By patch-clamp whole cell recording from Purkinje neurons in slices of young (5–9 days old) mouse cerebellum we have been able to isolate a tail current [ IK(ERG)] with the same characteristics as previously described for ERG channels. In zero external Ca2+ and high K+ (40 mM) the V1/2 of activation was –50.7 mV, the V1/2 of inactivation was –70.6 mV, and the deactivation rate was double exponential and voltage dependent. IK(ERG) was 93.0% blocked by WAY-123,398 (1 μM) and 78.2% by haloperidol (2 μM). The role of IK(ERG) on evoked firing was studied in adult mice, where WAY-123,398 application decreased the first spike latency, increased the firing frequency, and suppressed the frequency adaptation. However, the shape of individual action potentials was not affected. Stimulation of presynaptic climbing fibers evoked the Purkinje neuron “complex spike,” composed of an initial spike and several spikelets. IK(ERG) block caused an increase of the number of spikelets of the “complex spike.” These data show, for the first time, an IK(ERG) in a neuron of the CNS, the cerebellar Purkinje neuron, and indicate that such a current is involved in the control of membrane excitability, firing frequency adaptation, and in determining the effects of the climbing fiber synapse.