This Article Full Text Full Text (PDF) Methods Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Satin, J. Articles by Cribbs, L. L. Search for Related Content PubMed PubMed Citation Articles by Satin, J. Articles by Cribbs, L. L. Related Collections Remodeling Arrythmias-basic studies Gene expression Ion channels/membrane transport

(Circulation Research. 2000;86:636.)
© 2000 American Heart Association, Inc.

Cellular Biology

Identification of a T-Type Ca²⁺ Channel Isoform in Murine Atrial Myocytes (AT-1 Cells)

Jonathan Satin, Leanne L. Cribbs

From the Department of Physiology (J.S.), University of Kentucky College of Medicine, Lexington, Ky, and Department of Physiology and Cardiovascular Institute (L.L.C.), Loyola University Medical Center, Maywood, Ill.

Correspondence to Dr Jonathan Satin, Department of Physiology, MS-508, 800 Rose St, University of Kentucky College of Medicine, Lexington, KY 40536-0298. E-mail jsatin1{at}pop.uky.edu

Abstract—Calcium channels are important targets for therapeutics, but their molecular diversity complicates characterization of these channels in native heart cells. In this study, we identify a new splice variant of a low-voltage activated, or T-type Ca²⁺, channel in murine atrial myocytes. To date, 1G and 1H are the only 2 T-type Ca²⁺ channel isoforms found in cardiovascular tissue. We compared 1G and 1H channel current heterologously expressed in HEK 293 cells with T-type current from the murine atrial tumor cell, AT-1. AT-1 cell T-type current (I_T) has the same voltage dependence of activation and inactivation as 1G and 1H. The cloned T-type channels and AT-1 T-type current share similar kinetics of macroscopic inactivation and deactivation. The kinetics of recovery from inactivation of T-type currents serves as an electrophysiological signature for T-channel isoform. 1G and AT-1 I_T have a similar recovery from inactivation time course that is faster than that for 1H. In all cases, T-type current recovers with a biexponential time course, and the relative amplitude of fast and slow time courses explains the slower 1H recovery kinetics, rather than differences in the time constants of the individual transitions. Thus, the T-type channels may be an important contributor to automaticity in heart cells, and molecular diversity is reflected in the pathway of recovery from inactivation.

Key Words: Ca²⁺ channel • patch-clamp • electrophysiology • gating • atrial

This article has been cited by other articles:

				M. E. Mangoni and J. Nargeot Genesis and Regulation of the Heart Automaticity Physiol Rev, July 1, 2008; 88(3): 919 - 982. [Abstract] [Full Text] [PDF]

				H. Sun, D. Varela, D. Chartier, P. C. Ruben, S. Nattel, G. W. Zamponi, and N. Leblanc Differential Interactions of Na+ Channel Toxins with T-type Ca2+ Channels J. Gen. Physiol., July 1, 2008; 132(1): 101 - 113. [Abstract] [Full Text] [PDF]

				S. M. Crump, R. N. Correll, E. A. Schroder, W. C. Lester, B. S. Finlin, D. A. Andres, and J. Satin L-type calcium channel {alpha}-subunit and protein kinase inhibitors modulate Rem-mediated regulation of current Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1959 - H1971. [Abstract] [Full Text] [PDF]

				L. I. Brueggemann, B. L. Martin, J. Barakat, K. L. Byron, and L. L. Cribbs Low voltage-activated calcium channels in vascular smooth muscle: T-type channels and AVP-stimulated calcium spiking Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H923 - H935. [Abstract] [Full Text] [PDF]

				N. Niwa, K. Yasui, T. Opthof, H. Takemura, A. Shimizu, M. Horiba, J.-K. Lee, H. Honjo, K. Kamiya, and I. Kodama Cav3.2 subunit underlies the functional T-type Ca2+ channel in murine hearts during the embryonic period Am J Physiol Heart Circ Physiol, June 1, 2004; 286(6): H2257 - H2263. [Abstract] [Full Text] [PDF]

				J. Hering, A. Feltz, and R. C. Lambert Slow inactivation of the CaV3.1 isotype of T-type calcium channels J. Physiol., March 1, 2004; 555(2): 331 - 344. [Abstract] [Full Text] [PDF]

				S. C. Lee, Y. Hayashida, and A. T. Ishida Availability of Low-Threshold Ca2+ Current in Retinal Ganglion Cells J Neurophysiol, December 1, 2003; 90(6): 3888 - 3901. [Abstract] [Full Text] [PDF]

				B. S. Finlin, S. M. Crump, J. Satin, and D. A. Andres Regulation of voltage-gated calcium channel activity by the Rem and Rad GTPases PNAS, November 25, 2003; 100(24): 14469 - 14474. [Abstract] [Full Text] [PDF]

				E. Perez-Reyes Molecular Physiology of Low-Voltage-Activated T-type Calcium Channels Physiol Rev, January 1, 2003; 83(1): 117 - 161. [Abstract] [Full Text] [PDF]

				J. Chemin, A. Monteil, E. Perez-Reyes, E. Bourinet, J. Nargeot, and P. Lory Specific contribution of human T-type calcium channel isotypes ({alpha}1G, {alpha}1H and {alpha}1I) to neuronal excitability J. Physiol., April 1, 2002; 540(1): 3 - 14. [Abstract] [Full Text] [PDF]

				R. Kline, T. Jiang, X. Xu, V. O. Rybin, and S. F. Steinberg Abnormal calcium and protein kinase C-{epsilon} signaling in hypertrophied atrial tumor myocytes (AT-1 cells) Am J Physiol Heart Circ Physiol, June 1, 2001; 280(6): H2761 - H2769. [Abstract] [Full Text] [PDF]

				C.-C. Kuo and S. Yang Recovery from Inactivation of T-Type Ca2+ Channels in Rat Thalamic Neurons J. Neurosci., March 15, 2001; 21(6): 1884 - 1892. [Abstract] [Full Text] [PDF]

				L. L. Cribbs, B. L. Martin, E. A. Schroder, B. B. Keller, B. P. Delisle, and J. Satin Identification of the T-Type Calcium Channel (CaV3.1d) in Developing Mouse Heart Circ. Res., March 2, 2001; 88(4): 403 - 407. [Abstract] [Full Text] [PDF]

				C. R. Weber, K. S. Ginsburg, K. D. Philipson, T. R. Shannon, and D. M. Bers Allosteric Regulation of Na/Ca Exchange Current by Cytosolic Ca in Intact Cardiac Myocytes J. Gen. Physiol., February 1, 2001; 117(2): 119 - 132. [Abstract] [Full Text] [PDF]

				V. Leuranguer, A. Monteil, E. Bourinet, G. Dayanithi, and J. Nargeot T-type calcium currents in rat cardiomyocytes during postnatal development: contribution to hormone secretion Am J Physiol Heart Circ Physiol, November 1, 2000; 279(5): H2540 - H2548. [Abstract] [Full Text] [PDF]

				J. Nargeot A Tale of Two (Calcium) Channels Circ. Res., March 31, 2000; 86(6): 613 - 615. [Full Text] [PDF]

				C. Seisenberger, V. Specht, A. Welling, J. Platzer, A. Pfeifer, S. Kuhbandner, J. Striessnig, N. Klugbauer, R. Feil, and F. Hofmann Functional Embryonic Cardiomyocytes after Disruption of the L-type alpha 1C (Cav1.2) Calcium Channel Gene in the Mouse J. Biol. Chem., December 8, 2000; 275(50): 39193 - 39199. [Abstract] [Full Text] [PDF]