Alterations in dihydropyridine receptors in dystrophin-deficient cardiac muscle
Article
Article Title | Alterations in dihydropyridine receptors in dystrophin-deficient cardiac muscle |
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ERA Journal ID | 14581 |
Article Category | Article |
Authors | Woolf, Peter James (Author), Lu, Sai (Author), Cornford-Nairn, Renee A. (Author), Watson, Michael (Author), Xiao, Xiao-Hui (Author), Holroyd, Sean (Author), Brown, Lindsay (Author) and Hoey, Andrew (Author) |
Journal Title | American Journal of Physiology: Heart and Circulatory Physiology |
Journal Citation | 290 (6), pp. H2439-H2445 |
Number of Pages | 29 |
Year | 2006 |
Place of Publication | United States |
ISSN | 0363-6135 |
1522-1539 | |
Digital Object Identifier (DOI) | https://doi.org/10.1152/ajpheart.00844.2005 |
Abstract | 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. |
Keywords | Duchenne muscular dystrophy; calcium channels; heart |
ANZSRC Field of Research 2020 | 310999. Zoology not elsewhere classified |
Public Notes | Files associated with this item cannot be displayed due to copyright restrictions. |
Byline Affiliations | Centre for Biomedical Research |
University of Queensland |
https://research.usq.edu.au/item/9y3y3/alterations-in-dihydropyridine-receptors-in-dystrophin-deficient-cardiac-muscle
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