Gain of function mutants: ion channels and G protein-coupled receptors.

Abstract:

:Many ion channels and receptors display striking phenotypes for gain-of-function mutations but milder phenotypes for null mutations. Gain of molecular function can have several mechanistic bases: selectivity changes, gating changes including constitutive activation and slowed inactivation, elimination of a subunit that enhances inactivation, decreased drug sensitivity, changes in regulation or trafficking of the channel, or induction of apoptosis. Decreased firing frequency can occur via increased function of K+ or Cl- channels. Channel mutants also cause gain-of-function syndromes at the cellular and circuit level; of these syndromes, the cardiac long-QT syndromes are explained in a more straightforward way than are the epilepsies. G protein-coupled receptors are also affected by activating mutations.

journal_name

Annu Rev Neurosci

authors

Lester HA,Karschin A

doi

10.1146/annurev.neuro.23.1.89

keywords:

subject

Has Abstract

pub_date

2000-01-01 00:00:00

pages

89-125

eissn

0147-006X

issn

1545-4126

journal_volume

23

pub_type

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