抄録
The voltage-dependent CaV2.1 (P/Q-type) calcium channel is a predominant calcium channel in the central nervous system (CNS) and is an essential molecule for neurotransmitter release in presynaptic neurons and regulation of neuronal excitability and gene expression in postsynaptic neurons. Mutations in the gene encoding the CaV2.1 calcium channel α12.1 subunit are associated with neurological disorders in human and mice. In human, familial hemiplegic migraine, episodic ataxia type 2, spinocerebellar ataxia type 6 and others are associated with the α12.1 mutations. In mice, two major phenotypes of neurological disorders are cerebellar ataxia and absence epilepsy. Because several strains of the α12.1 subunit mutations are available, we have analyzed the impacts of the mutations on the channel properties, the synaptic transmission, the axonal extension, the network activity, and other factors, using the morphological and electrophysiological techniques. The analyses have provided insights into mechanisms how the symptoms of the genetic disorders become overt in some specific areas of CNS or in some developmental stages. The results will contribute to understanding the pathophysiology of human neurological disorders. An overview of the extensive results will be presented in the symposium. [Jpn J Physiol 55 Suppl:S8 (2005)]
