Abstract
Mice homozygous for targeted disruption of the α1A subunit of the voltage gated Ca channel (PQKO) show fatal ataxia and dystonia. We investigated properties of the cerebellar Purkinje cell (PC) in PQKO (P14-20) using acute cerebellar slices. PCs were patch-clamped at whole-cell mode and electrophysiologic/Ca imaging studies were performed in response to synaptic stimuli and somatic depolarization as well.In comparison with wild type littermates (WT), the magnitude of Ca transient (CaT) in PQKO PC induced by a train of parallel fiber stimuli (PF) was much smaller, whereas CaT evoked by climbing fiber (CF) was as large as that in WTs.Pharmacological studies revealed that compared to WT PF- and CF-EPSC in PQKO were more sensitive to w-conotoxin, an N-type Ca channel blocker, whereas deporalization-induced dendritic CaT was more sensitive to low-dose Ni2+, a T-type channel blocker. Overall, contribution of L-type channel was very little in PQKO and WT. These data suggest that the defect in P/Q-type Ca channel is not well conpensated at least in part, resulting in compromised Ca signaling in PC dendrites, and that the compensation mechanism is different between pre- and post synaptic sites in PCs. [Jpn J Physiol 55 Suppl:S148 (2005)]
