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

Xiao, Xiao-Hui and Woolf, Peter and Watson, Michael and Lu, Sai and Hoey, Andrew (2004) Alterations in cardiac dihydropyridine receptors and calcium channel function in MDX mice. In: ISHR 2004: 18th World Congress of the International Society for Heart Research, 7-11 Aug 2004, Brisbane, Australia.

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Abstract

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.


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Item Type: Conference or Workshop Item (Commonwealth Reporting Category E) (Paper)
Refereed: Yes
Item Status: Live Archive
Additional Information: Restricted access to published version in accordance with the copyright policy of the publisher. Abstract only published.
Faculty / Department / School: Historic - Faculty of Sciences - Department of Biological and Physical Sciences
Date Deposited: 30 Nov 2007 11:55
Last Modified: 15 May 2018 04:49
Uncontrolled Keywords: cardiac; cardiovascular systems; cell biology; mice
Fields of Research : 11 Medical and Health Sciences > 1109 Neurosciences > 110904 Neurology and Neuromuscular Diseases
06 Biological Sciences > 0601 Biochemistry and Cell Biology > 060107 Enzymes
11 Medical and Health Sciences > 1102 Cardiovascular Medicine and Haematology > 110201 Cardiology (incl. Cardiovascular Diseases)
Socio-Economic Objective: E Expanding Knowledge > 97 Expanding Knowledge > 970111 Expanding Knowledge in the Medical and Health Sciences
Identification Number or DOI: 10.1016/j.yjmcc.2004.05.003
URI: http://eprints.usq.edu.au/id/eprint/11565

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