Alterations in cardiac dihydropyridine receptors and calcium channel function in mdx mice

Xiao, X. H., Woolf, P., Watson, M., Lu, S. and Hoey, A. (2004). Alterations in cardiac dihydropyridine receptors and calcium channel function in mdx mice. In: Journal of Molecular And Cellular Cardiology: 2004 ISHR World Congress Meeting. 2004 ISHR World Congress Meeting, Brisbane, Australia, (176-176). 7-11 August, 2004. doi:10.1016/j.yjmcc.2004.05.003


Author Xiao, X. H.
Woolf, P.
Watson, M.
Lu, S.
Hoey, A.
Title of paper Alterations in cardiac dihydropyridine receptors and calcium channel function in mdx mice
Conference name 2004 ISHR World Congress Meeting
Conference location Brisbane, Australia
Conference dates 7-11 August, 2004
Proceedings title Journal of Molecular And Cellular Cardiology: 2004 ISHR World Congress Meeting   Check publisher's open access policy
Journal name Journal of Molecular and Cellular Cardiology   Check publisher's open access policy
Place of Publication London
Publisher Academic Press
Publication Year 2004
DOI 10.1016/j.yjmcc.2004.05.003
ISSN 0022-2828
Volume 37
Issue 1
Start page 176
End page 176
Total pages 1
Language eng
Abstract/Summary Duchenne muscular dystrophy (DMD) is a fatal neuromuscular condition affecting approximately one in 3500 live male births resulting from the lack of the myocyte protein dystrophin. The absence of dystrophin in cardiac myocytes is associated with calcium overload which in turn activates calcium-dependent proteolytic enzymes contributing to congestive heart failure, muscle necrosis and fibrosis. To date, the basis for the calcium overload has not been determined. Since L-type calcium channels are a major mediator of calcium influx we determined their potential contribution to the calcium overload. Male muscular dystrophy (mdx) mice and control C57BL10ScSn (C57) mice aged 12– 16 weeks were used in all experiments. In tissue bath studies, isolated contracting left atria from mdx revealed a reduced potency to the dihydropyridine (DHP) agonist BayK8644 and antagonist nifedipine (P < 0.05). Similarly, radioligand binding studies using the DHP antagonist [3H]-PN 200-110 showed a reduced potency (P < 0.05) in isolated membranes, associated with an increased receptor density (P < 0.05). The increased receptor density was supported by RT-PCR experiments revealing increased RNAfor the DHP receptor. Patch clamp studies revealed the presence of a diltiazem sensitive calcium current that showed delayed inactivation in isolated mdx myocytes (P < 0.01). In conclusion, the increased number of DHP binding sites and the delay in L-type current inactivation may both contribute to increased calcium influx and hence calcium overload in the dystrophin deficient mdx cardiac myocytes.
Subjects 11 Medical and Health Sciences
Keyword Cardiac & Cardiovascular Systems
Cell Biology
Q-Index Code EX
Q-Index Status Provisional Code
Institutional Status Unknown

 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 0 times in Thomson Reuters Web of Science Article
Google Scholar Search Google Scholar
Created: Tue, 14 Aug 2007, 00:29:50 EST