Abstract
What do epilepsy, migraine headache, episodic ataxia, peryodic paralysis, malignant hyperthermia, night blindness have in common? These human neurological disorders can be caused by mutations in genes encoding ion channels, and therefore can be considered as “channelopathies”, a term used here to name inherited ion channel pathologies. More specifically, they can be considered as calcium channelopathies since they can be caused by mutations in genes encoding calcium channels. This chapter deals with known human and mouse calcium channelopathies of the central nervous system (CNS). The human diseases comprise (i) a recessive retinal disorder, X-linked congenital stationary night blindness (xlCSNB), associated with mutations in the CACNA1F gene, encoding the pore-forming subunit of an L-type voltage-dependent calcium channel expressed only in the retina, and (ii) a group of rare allelic autosomal dominant human neurological disorders including familial hemiplegic migraine (FHM), episodic ataxia type 2 (EA-2) and spinocerebellar ataxia type 6 (SCA6), all associated with mutations in the CACNA1A gene, encoding the pore-forming subunit of neuronal P/Q-type voltage-dependent calcium channels. Mutations at the mouse orthologue of the CACNA1A gene cause a group of recessive neurological disorders, including the tottering and leaner phenotypes with ataxia and absence epilepsy, and the rolling Nagoya phenotype with ataxia without seizures. Two other spontaneous mouse mutants with ataxia and absence epilepsy, lethargic and stargazer, have mutations in genes encoding a calcium channel auxiliary β subunit and a putative calcium channel auxiliary γ subunit. The skeletal muscle human calcium channelopathies hypokalemic peryodic paralysis and malignant hyperthermia will not be dealt with here.
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Pietrobon, D. (2000). Calcium Channelopathies in Nervous System. In: Pochet, R., Donato, R., Haiech, J., Heizmann, C., Gerke, V. (eds) Calcium: The Molecular Basis of Calcium Action in Biology and Medicine. Springer, Dordrecht. https://doi.org/10.1007/978-94-010-0688-0_23
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