The L-type Ca(2+) channel as a therapeutic target in heart disease.
The L-type Ca(2+) 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 Ca(2+) channel also regulates cytoplasmic calcium levels. It is well recognised 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 Ca(2+) 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 ischemia-reperfusion injury, cardiac hypertrophy or cardiac failure providing good evidence that the L-type Ca(2+) channel may be an efficacious target in the prevention of cardiac pathology.
Viola
H M
HM
The University of Western Australia and The Western Australian Institute for Medical Research, Crawley, Western Australia.
Macdonald
W A
WA
Tang
H
H
Hool
L C
LC
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000627:therapeutic use; D020746:Calcium Channels, L-Type / Q000378:metabolism* / Q000502:physiology; D006332:Cardiomegaly / Q000473:pathology; D004285:Dogs; D006331:Heart Diseases / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008969:Molecular Sequence Data; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000633:toxicity; D015398:Signal Transduction
D002120:Calcium Channel Agonists; D020746:Calcium Channels, L-Type; D017382:Reactive Oxygen Species; D002118:Calcium