Two distinct sets of Ca 2+ and K + channels are activated at different membrane potentials by the climbing fiber synaptic potential in Purkinje neuron dendrites

Abstract

In cerebellar Purkinje neuron dendrites, the transient depolarization associated with a climbing fiber (CF) EPSP activates voltage-gated Ca 2+ channels (VGCCs), voltage-gated K + channels (VGKCs), and Ca 2+ -activated SK and BK K + channels. The resulting membrane potential (V m ) and Ca 2+ transients play a fundamental role in dendritic integration and synaptic plasticity of parallel fiber inputs. Here we report a detailed investigation of the kinetics of dendritic Ca 2+ and K + channels activated by CF-EPSPs, based on optical measurements of V m and Ca 2+ transients and on a single-compartment NEURON model reproducing experimental data. We first measured V m and Ca 2+ transients associated with CF-EPSPs at different initial V m , and we analyzed the changes in the Ca 2+ transients produced by the block of each individual VGCCs, of A-type VGKCs and of SK and BK channels. Then, we constructed a model that includes six active ion channels to accurately match experimental signals and extract the physiological kinetics of each channel. We found that two different sets of channels are selectively activated. When the dendrite is hyperpolarized, CF-EPSPs mainly activate T-type VGCCs, SK channels, and A-type VGKCs that limit the transient V m ∽<0 mV. In contrast, when the dendrite is depolarized, T-type VGCCs and A-type VGKCs are inactivated and CF-EPSPs activate P/Q-type VGCCs, high-voltage activated VGKCs, and BK channels, leading to Ca 2+ spikes. Thus, the potentially activity-dependent regulation of A-type VGKCs, controlling the activation of this second set of channels, is likely to play a crucial role in signal integration and plasticity in Purkinje neuron dendrites.