Alterations in dihydropyridine receptors in dystrophin-deficient cardiac muscle

Woolf, Peter J., Lu, Sai, Cornford-Nairn, Renee, Watson, Michael, Xiao, Xiao-Hui, Holroyd, Sean M., Brown, Lindsay and Hoey, Andrew J. (2006) Alterations in dihydropyridine receptors in dystrophin-deficient cardiac muscle. American Journal of Physiology: Heart and Circulatory Physiology, 290 6: H2439.1-H2445.7.


Author Woolf, Peter J.
Lu, Sai
Cornford-Nairn, Renee
Watson, Michael
Xiao, Xiao-Hui
Holroyd, Sean M.
Brown, Lindsay
Hoey, Andrew J.
Title Alterations in dihydropyridine receptors in dystrophin-deficient cardiac muscle
Journal name American Journal of Physiology: Heart and Circulatory Physiology  (ERA 2012 Listed)    (ERA 2010 Rank A)   Check publisher's open access policy
Publication date 2006
Sub-type Article
DOI 10.1152/ajpheart.00844.2005
Volume number 290
Issue number 6
ISSN 0363-6135
1522-1539
Start page H2439.1
End page H2445.7
Total pages 7
Editor Brenda B Rauner
Alberto Nasjletti
Place of publication Bethesda, MD, United States
Publisher American Physiological Society
Collection year 2006
Language eng
Subject C1
320502 Basic Pharmacology
730106 Cardiovascular system and diseases
Abstract The deficiency of dystrophin, a critical membrane stabilizing 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 BAY K 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) were 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 blot analysis 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.
Keyword Duchenne muscular dystrophy
Calcium channels
Heart
Cardiac & cardiovascular systems
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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