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(Circulation Research. 2004;95:337.)
© 2004 American Heart Association, Inc.

Editorials

Blocking the L-type Ca²⁺ Channel With a Gem

A Paradigm for a More Specific Ca²⁺ Channel Blocker

Ravi C. Balijepalli, Jason D. Foell, Timothy J. Kamp

From the Department of Medicine, University of Wisconsin-Madison.

Correspondence to Timothy J. Kamp, H6/343 Clinical Science Center, Box 3248, 600 Highland Ave, Madison, WI 53792. E-mail tjk@medicine. wisc.edu

Key Words: gene therapy • calcium channel blocker • Gem • RGK protein • L-type Ca²⁺ channel

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Ca²⁺ channel blockers have been an important part of the cardiovascular pharmacological armamentarium for more than 2 decades. These agents were developed as antianginals and antihypertensives, but their indications have expanded to include treatment of certain arrhythmias because of their atrioventricular (AV) nodal blocking properties. Interestingly, the development of these compounds largely preceded our knowledge of the molecular composition and detailed functional properties of voltage-gated Ca²⁺ channels. In fact, Ca²⁺ channel blockers were critical in defining the distinct class of voltage-dependent Ca²⁺ channels referred to as L-type Ca²⁺ channels, which can be found in cardiac myocytes, skeletal myocytes, vascular smooth muscle cells, neurons, and endocrine cells among other cells. Despite this broad distribution of L-type Ca²⁺ channels, Ca²⁺ channel blockers have proven useful agents because they exhibit pharmacological specificity for vascular smooth muscle and cardiac muscle. This specificity is attributable to a variety of factors including the voltage and use-dependent blocking properties of these agents, subtle differences in the sensitivity of distinct isoforms of L-type Ca²⁺ channels present in different tissues, and the tissue distribution of the drugs. In addition, different classes of Ca²⁺ channel blockers vary in their relative potency to block vascular smooth muscle Ca²⁺ channels (antihypertensive/antianginal properties) relative to their block of AV nodal Ca²⁺ channels (antiarrhythmic properties). Alas, the specificity is not perfect, and so these agents can bring with them undesired side effects including constipation, peripheral edema, dizziness, and headache. In addition, problems can arise from the overlap of vascular smooth muscle and cardiac blocking . . . [Full Text of this Article]

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