PubMed 19729018

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Cav3.1 , Cav3.2

Title: Cardiac T-type Ca(2+) channels in the heart.

Authors: Kyoichi Ono, Toshihiko Iijima

Journal, date & volume: J. Mol. Cell. Cardiol., 2010 Jan , 48, 65-70

PubMed link:

Two different Ca(2+) channels exist in cardiac myocytes. While the L-type Ca(2+) channel is ubiquitous and the main source of Ca(2+) for excitation-contraction coupling and pacemaker activity, the functional role of the T-type Ca(2+) channel is diverse and depends on mammalian species, heart region, age and various cardiac diseases. Two isoforms of T-type Ca(2+) channel proteins in the heart, Ca(V)3.1 and Ca(V)3.2, are functionally expressed in embryonic hearts, but markedly diminish during development. In the adult heart, the T-type Ca(2+) channel is almost undetectable in ventricular myocytes and is most prevalent in the conduction system, playing a functional role in facilitating pacemaker depolarization of the sinoatrial node. Interestingly, the T-type Ca(2+) channel is re-expressed in atrial and ventricular myocytes under various pathological conditions such as hypertrophy and heart failure, and contributes to abnormal electrical activity and excitation-contraction coupling, but the T-type channel provides a smaller contribution to the trigger for Ca(2+) release than does the L-type Ca(2+) channel. Instead, the T-type Ca(2+) channel has been shown to play a crucial role in the process of pathological cardiac hypertrophy. Increased Ca(2+) influx via Ca(V)3.2, the T-type Ca(2+) channel, induces calcineurin/NFAT (nuclear factor of activated T-cell) hypertrophic signaling. Furthermore, new evidence has been accumulating on the regulatory mechanism of T-type Ca(2+) channel expression, including the neuron restrictive silencer element-neuron restrictive silencer factor (NRSE-NRSF) system, mitogen activated protein (MAP) kinases and cardiac homeobox transcription factor Csx/Nkx2.5. This review summarizes our present knowledge regarding cardiac T-type Ca(2+) channels, and discusses their pathophysiological significance in the heart.