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
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Identification Number or DOI: doi: 10.1152/ajpheart.00844.2005
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.
|Item Type:||Article (Commonwealth Reporting Category C)|
|Additional Information:||Permanent restricted access to paper due to publisher copyright restrictions.|
|Uncontrolled Keywords:||Duchenne muscular dystrophy; calcium channels; heart|
|Fields of Research (FOR2008):||06 Biological Sciences > 0606 Physiology > 060699 Physiology not elsewhere classified|
|Subjects:||270000 Biological Sciences > 270600 Physiology > 270699 Physiology not elsewhere classified|
|Socio-Economic Objective (SEO2008):||UNSPECIFIED|
|Deposited On:||11 Oct 2007 11:13|
|Last Modified:||23 May 2012 11:22|
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