Zebrafish as a Model System for the Study of Severe CaV2.1 (α1A) Channelopathies
JournalFrontiers in Molecular Neuroscience
PublisherFrontiers Media S.A.
MetadataShow full item record
AbstractThe P/Q-type CaV2.1 channel regulates neurotransmitter release at neuromuscular junctions (NMJ) and many central synapses. CACNA1A encodes the pore-containing α1A subunit of CaV2.1 channels. In humans, de novo CACNA1A mutations result in a wide spectrum of neurological, neuromuscular, and movement disorders, such as familial hemiplegic migraine type 1 (FHM1), episodic ataxia type 2 (EA2), as well as a more recently discovered class of more severe disorders, which are characterized by ataxia, hypotonia, cerebellar atrophy, and cognitive/developmental delay. Heterologous expression of CaV2.1 channels has allowed for an understanding of the consequences of CACNA1A missense mutations on channel function. In contrast, a mechanistic understanding of how specific CACNA1A mutations lead in vivo to the resultant phenotypes is lacking. In this review, we present the zebrafish as a model to both study in vivo mechanisms of CACNA1A mutations that result in synaptic and behavioral defects and to screen for effective drug therapies to combat these and other CaV2.1 channelopathies. Copyright 2020 Tyagi, Ribera and Bannister.
SponsorsThis work was supported by National Institute of Neurological Disorders and Stroke/National Institute of Health (NIH) grants NS103777 and NS086839 to RB and AR, respectively. ST was supported by the Boettcher Foundation.
episodic ataxia type 2
familial hemiplegic migraine type 1
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85079755669&doi=10.3389%2ffnmol.2019.00329&partnerID=40&md5=de5a7db47ffdffe5aa086d7f376f39e5; http://hdl.handle.net/10713/12160