Alterations in Dihydropyridine Receptors in Dystrophin-deficient Cardiac Muscle.
From: Centre for Biomedical Research, Faculty of Sciences, University of Southern Queensland, Toowoomba, 4350 Queensland, Australia.
American journal of physiology. Heart and circulatory physiology
- Publish Date: Jun 2006
- ISSN: 0363-6135
- Volume: 290
- Issue: 6
- Pages: H2439-45
- Medium: Print
- Language: English
- Citation (JAMA): Woolf Peter J, Lu Sai, Cornford-Nairn Renee, et al. Alterations in Dihydropyridine Receptors in Dystrophin-deficient Cardiac Muscle.. Am. J. Physiol. Heart Circ. Physiol. Jun 2006;290:H2439-45
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.
Mesh Headings (Keywords): 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester, Animals, Blotting, Western, Calcium, Calcium Channel Agonists, Calcium Channel Blockers, Calcium Channels, L-Type, Calcium Signaling, Dystrophin, Electrophysiology, Heart, Mice, Mice, Inbred C57BL, Mice, Inbred mdx, Myocardial Contraction, Nifedipine, Patch-Clamp Techniques, Radioligand Assay, Reverse Transcriptase Polymerase Chain Reaction
Check for Full Text / PubMed Unique Identifier (PMID): 16415078
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