Premium
Robust L‐type calcium current expression following heterozygous knockout of the Cav1.2 gene in adult mouse heart
Author(s) -
Rosati Barbara,
Yan Qinghong,
Lee Mi Sun,
Liou ShianRen,
Ingalls Brian,
Foell Jason,
Kamp Timothy J.,
McKin David
Publication year - 2011
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2011.210237
Subject(s) - knockout mouse , cav1.2 , ventricle , gene knockout , medicine , endocrinology , contractility , calcium channel , gene expression , voltage dependent calcium channel , wild type , biology , allele , cre recombinase , cardiac function curve , transgene , gene , calcium , genetically modified mouse , heart failure , mutant , genetics
Non‐technical summary Appropriate regulation of ion channel expression is critical for the maintenance of both electrical stability and normal contractile function in the heart. A classic way to study the robustness of biological systems is to examine the effects of changes in gene dosage. We have studied how the heart responds to changes in the L‐type calcium channel gene dosage. Homozygous Cav1.2 knockout in the adult heart is lethal, without compensatory responses in expression of other calcium channel genes. Following heterozygous knockout, Cav1.2 mRNA levels are not buffered, Cav1.2 membrane protein levels are partly buffered and L‐type calcium current expression is relatively well buffered. These data are consistent with a passive model of Cav1.2 biosynthesis that includes saturated steps, which act to buffer Cav1.2 protein and L‐type calcium current expression. The results suggest that there is little or no homeostatic regulation of calcium current expression in either heterozygous or homozygous knockout mice.