Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Mar 15;304(6):H767-75.
doi: 10.1152/ajpheart.00700.2012. Epub 2013 Jan 18.

L-type Ca(2+) channel contributes to alterations in mitochondrial calcium handling in the mdx ventricular myocyte

Helena M Viola  1 , Stefan M K Davies, Aleksandra Filipovska, Livia C Hool
Affiliations
Free article

L-type Ca(2+) channel contributes to alterations in mitochondrial calcium handling in the mdx ventricular myocyte

Helena M Viola et al. Am J Physiol Heart Circ Physiol. .
Free article

Abstract

The L-type Ca(2+) channel is the main route for calcium entry into cardiac myocytes, and it is essential for contraction. Alterations in whole cell L-type Ca(2+) channel current and Ca(2+) homeostasis have been implicated in the development of cardiomyopathies. Cytoskeletal proteins can influence whole cell L-type Ca(2+) current and mitochondrial function. Duchenne muscular dystrophy is a fatal X-linked disease that leads to progressive muscle weakness due to the absence of cytoskeletal protein dystrophin. This includes dilated cardiomyopathy, but the mechanisms are not well understood. We sought to identify the effect of alterations in whole cell L-type Ca(2+) channel current on mitochondrial function in the murine model of Duchenne muscular dystrophy (mdx). Activation of the L-type Ca(2+) channel with the dihydropyridine agonist BayK(-) caused a significantly larger increase in cytosolic Ca(2+) in mdx vs. wild-type (wt) ventricular myocytes. Consistent with elevated cytosolic Ca(2+), resting mitochondrial Ca(2+), NADH, and mitochondrial superoxide were significantly greater in mdx vs. wt myocytes. Activation of the channel with BayK(-) caused a further increase in mitochondrial Ca(2+), NADH, and superoxide in mdx myocytes. The ratios of the increases were similar to the ratios recorded in wt myocytes. In mitochondria isolated from 8-wk-old mdx hearts, respiration and mitochondrial electron transport chain complex activity were similar to mitochondria isolated from wt hearts. We conclude that mitochondria function at a higher level of resting calcium in the intact mdx myocyte and activation of the L-type Ca(2+) channel contributes to alterations in calcium handling by the mitochondria. This perturbation may contribute to the development of cardiomyopathy.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

Substances

LinkOut - more resources