Alterations in dihydropyridine receptors in dystrophin-deficient cardiac muscle

Woolf, Peter James and Lu, Sai and Cornford-Nairn, Renee A. and Watson, Michael and Xiao, Xiao-Hui and Holroyd, Sean and Brown, Lindsay and Hoey, Andrew (2006) Alterations in dihydropyridine receptors in dystrophin-deficient cardiac muscle. American Journal of Physiology: Heart and Circulatory Physiology, 290 (6). H2439-H2445. ISSN 0363-6135


The deficiency of dystrophin, a critical membrane stabilising protein, in the mdx mouse causes an elevation in intracellular calcium in myocytes. One mechanism that could elicit increases in intracellular calcium is enhanced influx via the L-type calcium channels. This study investigated the effects of the dihydropyridines BayK 8644 and nifedipine and alterations in dihydropyridine receptors in dystrophin-deficient mdx hearts. A lower force of contraction and a reduced potency of extracellular calcium (P<0.05) was evident in mdx left atria. The dihydropyridine agonist Bay K 8644 and antagonist nifedipine had 2.7 and 1.9 fold lower potencies in contracting left atria (P<0.05). This corresponded with a 2.0 fold reduction in dihydropyridine receptor affinity evident from radioligand binding studies of mdx ventricular homogenates (P<0.05). Increased ventricular dihydropyridine receptor protein was evident from both radioligand binding studies and Western blots and was accompanied by increased mRNA levels (P<0.05). Patch clamp studies in isolated ventricular myocytes showed no change in L-type calcium current density, but revealed delayed channel inactivation (P<0.05). This study indicates that a deficiency of dystrophin leads to changes in dihydropyridine receptors and L-type calcium channel properties that may contribute to enhanced calcium influx. Increased influx is a potential mechanism for the calcium overload observed in dystrophin deficient cardiac muscle.

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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: Permanent restricted access to paper due to publisher copyright restrictions.
Faculty / Department / School: Historic - Faculty of Sciences - Department of Biological and Physical Sciences
Date Deposited: 11 Oct 2007 01:13
Last Modified: 02 Jul 2013 22:46
Uncontrolled Keywords: Duchenne muscular dystrophy; calcium channels; heart
Fields of Research : 06 Biological Sciences > 0606 Physiology > 060699 Physiology not elsewhere classified
Identification Number or DOI: 10.1152/ajpheart.00844.2005

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