Functional importance of T-type voltage-gated calcium channels in the cardiovascular and renal system: news from the world of knockout mice.

Abstract

Over the years, it has been discussed whether T-type calcium channels Cav3 play a role in the cardiovascular and renal system. T-type channels have been reported to play an important role in renal hemodynamics, contractility of resistance vessels, and pacemaker activity in the heart. However, the lack of highly specific blockers cast doubt on the conclusions. As new T-type channel antagonists are being designed, the roles of T-type channels in cardiovascular and renal pathology need to be elucidated before T-type blockers can be clinically useful. Two types of T-type channels, Cav3.1 and Cav3.2, are expressed in blood vessels, the kidney, and the heart. Studies with gene-deficient mice have provided a way to investigate the Cav3.1 and Cav3.2 channels and their role in the cardiovascular system. This review discusses the results from these knockout mice. Evaluation of the literature leads to the conclusion that Cav3.1 and Cav3.2 channels have important, but different, functions in mice. T-type Cav3.1 channels affect heart rate, whereas Cav3.2 channels are involved in cardiac hypertrophy. In the vascular system, Cav3.2 activation leads to dilation of blood vessels, whereas Cav3.1 channels are mainly suggested to affect constriction. The Cav3.1 channel is also involved in neointima formation following vascular damage. In the kidney, Cav3.1 regulates plasma flow and Cav3.2 plays a role setting glomerular filtration rate. In conclusion, Cav3.1 and Cav3.2 are new therapeutic targets in several cardiovascular pathologies, but the use of T-type blockers should be specifically directed to the disease and to the channel subtype.