Cardiac T-type Ca(2+) channels in the heart.
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.
Ono
Kyoichi
K
Department of Cell Physiology, Akita University School of Medicine, Akita 010-8543, Japan. onok@med.akita-u.ac.jp
Iijima
Toshihiko
T
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000235:genetics / Q000378:metabolism*; D006332:Cardiomegaly / Q000378:metabolism; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism*
D020747:Calcium Channels, T-Type