Regulation of gene transcription by voltage-gated L-type calcium channel, Cav1.3.

Autor:	Lu L; From the Department of Internal Medicine, Division of Cardiovascular Medicine, University of California, Davis, California 95616,; the College of Life Sciences, Nanjing Normal University, Nanjing 210046, China. Electronic address: linglu@njnu.edu.cn., Sirish P; From the Department of Internal Medicine, Division of Cardiovascular Medicine, University of California, Davis, California 95616., Zhang Z; From the Department of Internal Medicine, Division of Cardiovascular Medicine, University of California, Davis, California 95616., Woltz RL; From the Department of Internal Medicine, Division of Cardiovascular Medicine, University of California, Davis, California 95616., Li N; From the Department of Internal Medicine, Division of Cardiovascular Medicine, University of California, Davis, California 95616., Timofeyev V; From the Department of Internal Medicine, Division of Cardiovascular Medicine, University of California, Davis, California 95616., Knowlton AA; From the Department of Internal Medicine, Division of Cardiovascular Medicine, University of California, Davis, California 95616,; the Department of Veterans Affairs, Northern California Health Care System, Mather, California 95655., Zhang XD; From the Department of Internal Medicine, Division of Cardiovascular Medicine, University of California, Davis, California 95616., Yamoah EN; the Department of Physiology, School of Medicine, University of Nevada, Reno, Nevada 89557, and. Electronic address: enyamoah@gmail.com., Chiamvimonvat N; From the Department of Internal Medicine, Division of Cardiovascular Medicine, University of California, Davis, California 95616,; the Department of Veterans Affairs, Northern California Health Care System, Mather, California 95655,. Electronic address: nchiamvimonvat@ucdavis.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2015 Feb 20; Vol. 290 (8), pp. 4663-4676. Date of Electronic Publication: 2014 Dec 23.
DOI:	10.1074/jbc.M114.586883
Abstrakt:	Cav1.3 L-type Ca(2+) channel is known to be highly expressed in neurons and neuroendocrine cells. However, we have previously demonstrated that the Cav1.3 channel is also expressed in atria and pacemaking cells in the heart. The significance of the tissue-specific expression of the channel is underpinned by our previous demonstration of atrial fibrillation in a Cav1.3 null mutant mouse model. Indeed, a recent study has confirmed the critical roles of Cav1.3 in the human heart (Baig, S. M., Koschak, A., Lieb, A., Gebhart, M., Dafinger, C., Nürnberg, G., Ali, A., Ahmad, I., Sinnegger-Brauns, M. J., Brandt, N., Engel, J., Mangoni, M. E., Farooq, M., Khan, H. U., Nürnberg, P., Striessnig, J., and Bolz, H. J. (2011) Nat. Neurosci. 14, 77-84). These studies suggest that detailed knowledge of Cav1.3 may have broad therapeutic ramifications in the treatment of cardiac arrhythmias. Here, we tested the hypothesis that there is a functional cross-talk between the Cav1.3 channel and a small conductance Ca(2+)-activated K(+) channel (SK2), which we have documented to be highly expressed in human and mouse atrial myocytes. Specifically, we tested the hypothesis that the C terminus of Cav1.3 may translocate to the nucleus where it functions as a transcriptional factor. Here, we reported for the first time that the C terminus of Cav1.3 translocates to the nucleus where it functions as a transcriptional regulator to modulate the function of Ca(2+)-activated K(+) channels in atrial myocytes. Nuclear translocation of the C-terminal domain of Cav1.3 is directly regulated by intracellular Ca(2+). Utilizing a Cav1.3 null mutant mouse model, we demonstrate that ablation of Cav1.3 results in a decrease in the protein expression of myosin light chain 2, which interacts and increases the membrane localization of SK2 channels. (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)
Databáze:	MEDLINE
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