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The L-Type Ca2+ Channel as a Therapeutic Target in Heart Disease

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Abstract:

The L-type Ca2+ channel plays a critical role in cardiac function as the main route for entry of calcium into cardiac myocytes. It is essential to excitability as it shapes the long plateau phase of the cardiac action potential that is unique to cardiac ventricular myocytes. It is necessary for contraction as it triggers the release of calcium from sarcoplasmic reticulum stores for actin-myosin interaction. The L-type Ca2+ channel also regulates cytoplasmic calcium levels. It is well recognized that an increase in intracellular calcium is involved in the activation of growth-promoting signal pathways. Recently, reactive oxygen species have been implicated in the activation of signal pathways and the development of pathological hypertrophy. There is now evidence that implicates activation of the L-type Ca2+ channel with persistent alterations in calcium homeostasis and cellular reactive oxygen species production as a possible trigger of cardiac hypertrophy. A number of different approaches have been used to modify channel function with the view to preventing ischemiareperfusion injury, cardiac hypertrophy or cardiac failure providing good evidence that the L-type Ca2+ channel may be an efficacious target in the prevention of cardiac pathology.

Keywords: L-type Ca2+ channel; L-type Ca2+ channel antagonists; calcium homeostasis; cardiac hypertrophy; reactive oxygen species

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986709789057671

Affiliations: Physiology M311, School of Biomedical, Biomolecular and Chemical Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia.

Publication date: September 1, 2009

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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