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Distinct contributions of small and large conductance Ca²⁺-activated K⁺ channels to rat Purkinje neuron function

Jeremy R. Edgerton and Peter H. Reinhart

The cerebellum is important for many aspects of behaviour, from posture maintenance and goal-oriented reaching movements to timing tasks and certain forms of learning. In every case, information flowing through the cerebellum passes through Purkinje neurons, which receive input from the two primary cerebellar afferents and generate continuous streams of action potentials that constitute the sole output from the cerebellar cortex to the deep nuclei. The tonic firing behaviour observed in Purkinje neurons in vivo is maintained in brain slices even when synaptic inputs are blocked, suggesting that Purkinje neuron activity relies to a significant extent on intrinsic conductances. Previous research has suggested that the interplay between Ca²⁺ currents and Ca²⁺-activated K⁺ channels (K_Ca channels) is important for Purkinje cell activity, but how many different K_Ca channel types are present and what each channel type contributes to cell behaviour remains unclear. In order to better understand the ionic mechanisms that control the behaviour of these neurons, we investigated the effects of different Ca²⁺ channel and K_Ca channel antagonists on Purkinje neurons in acute slices of rat cerebellum. Our data show that Ca²⁺ entering through P-type voltage-gated Ca²⁺ channels activates both small-conductance (SK) and large-conductance (BK) K_Ca channels. SK channels play a role in setting the intrinsic firing frequency, while BK channels regulate action potential shape and may contribute to the unique climbing fibre response.

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