Aberrant Splicing Promotes Proteasomal Degradation of L-type Ca_V1.2 Calcium Channels by Competitive Binding for Ca_Vβ Subunits in Cardiac Hypertrophy.

ABSTRACT: Decreased expression and activity of Ca_V1.2 calcium channels has been reported in pressure overload-induced cardiac hypertrophy and heart failure. However, the underlying mechanisms remain unknown. Here we identified in rodents a splice variant of Ca_V1.2 channel, named Ca_V1.2_e21+22, that contained the pair of mutually exclusive exons 21 and 22. This variant was highly expressed in neonatal hearts. The abundance of this variant was gradually increased by 12.5-folds within 14 days of transverse aortic banding that induced cardiac hypertrophy in adult mouse hearts and was also elevated in left ventricles from patients with dilated cardiomyopathy. Although this variant did not conduct Ca²⁺ ions, it reduced the cell-surface expression of wi

SUBMITTER: Hu Z 

PROVIDER: S-EPMC5059693 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature