What can naturally occurring mutations tell us about Ca(v)1.x channel function?
Biochim Biophys Acta
; 1828(7): 1598-607, 2013 Jul.
Article
em En
| MEDLINE
| ID: mdl-23219801
ABSTRACT
Voltage-gated Ca²âº channels allow for Ca²âº-dependent intracellular signaling by directly mediating Ca²âº ion influx, by physical coupling to intracellular Ca²âº release channels or functional coupling to other ion channels such as Ca²âº activated potassium channels. L-type Ca²âº channels that comprise the family of Ca(v)1 channels are expressed in many electrically excitable tissues and are characterized by their unique sensitivity to dihydropyridines. In this issue, we summarize genetic defects in L-type Ca²âº channels and analyze their role in human diseases (Ca²âº channelopathies); e.g. mutations in Ca(v)1.2 α1 cause Timothy and Brugada syndrome, mutations in Ca(v)1.3 α1 are linked to sinoatrial node dysfunction and deafness while mutations in Ca(v)1.4 α1 are associated with X-linked retinal disorders such as an incomplete form of congenital stationary night blindness. Herein, we also put the mutations underlying the channel's dysfunction into the structural context of the pore-forming α1 subunit. This analysis highlights the importance of combining functional data with structural analysis to gain a deeper understanding for the disease pathophysiology as well as for physiological channel function. This article is part of a Special Issue entitled Calcium channels.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Ativação do Canal Iônico
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Cálcio
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Canais de Cálcio Tipo L
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Canalopatias
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Mutação
Limite:
Humans
Idioma:
En
Revista:
Biochim Biophys Acta
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Áustria