Biophys J, December 2000, p. 3052-3062, Vol. 79, No. 6

Mg²⁺ Block Unmasks Ca²⁺/Ba²⁺ Selectivity of 1G T-Type Calcium Channels

Jose R. Serrano,^* Shervin R. Dashti,^* Edward Perez-Reyes, and Stephen W. Jones^*

 ^*Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106; and  Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908 USA

We have examined permeation by Ca²⁺ and Ba²⁺, and block by Mg²⁺, using whole-cell recordings from 1G T-type calcium channels stably expressed in HEK 293 cells. Without Mg_o²⁺, inward currents were comparable with Ca²⁺ and Ba²⁺. Surprisingly, three other results indicate that 1G is actually selective for Ca²⁺ over Ba²⁺. 1) Mg²⁺ block is ~7-fold more potent with Ba²⁺ than with Ca²⁺. With near-physiological (1 mM) Mg_o²⁺, inward currents were ~3-fold larger with 2 mM Ca²⁺ than with 2 mM Ba²⁺. The stronger competition between Ca²⁺ and Mg²⁺ implies that Ca²⁺ binds more tightly than Ba²⁺. 2) Outward currents (carried by Na⁺) are blocked more strongly by Ca²⁺ than by Ba²⁺. 3) The reversal potential is more positive with Ca²⁺ than with Ba²⁺, thus P_Ca > P_Ba. We conclude that 1G can distinguish Ca²⁺ from Ba²⁺, despite the similar inward currents in the absence of Mg_o²⁺. Our results can be explained by a 2-site, 3-barrier model if Ca²⁺ enters the pore 2-fold more easily than Ba²⁺ but exits the pore at a 2-fold lower rate.

Biophys J, December 2000, p. 3052-3062, Vol. 79, No. 6
© 2000 by the Biophysical Society   0006-3495/00/12/3052/11  $2.00

This article has been cited by other articles:

				C. A. Obejero-Paz, I. P. Gray, and S. W. Jones Ni2+ Block of CaV3.1 ({alpha}1G) T-type Calcium Channels J. Gen. Physiol., August 1, 2008; 132(2): 239 - 250. [Abstract] [Full Text] [PDF]

				N. Khan, I. P. Gray, C. A. Obejero-Paz, and S. W. Jones Permeation and Gating in CaV3.1 ({alpha}1G) T-type Calcium Channels Effects of Ca2+, Ba2+, Mg2+, and Na+ J. Gen. Physiol., August 1, 2008; 132(2): 223 - 238. [Abstract] [Full Text] [PDF]

				K. C. Bittner and D. A. Hanck The Relationship between Single-Channel and Whole-Cell Conductance in the T-type Ca2+ Channel CaV3.1 Biophys. J., July 15, 2008; 95(2): 931 - 941. [Abstract] [Full Text] [PDF]

				T. Cens, M. Rousset, A. Kajava, and P. Charnet Molecular Determinant for Specific Ca/Ba Selectivity Profiles of Low and High Threshold Ca2+ Channels J. Gen. Physiol., September 24, 2007; 130(4): 415 - 425. [Abstract] [Full Text] [PDF]

				H.-S. Sun, K. Hui, D. W. K. Lee, and Z.-P. Feng Zn2+ Sensitivity of High- and Low-Voltage Activated Calcium Channels Biophys. J., August 15, 2007; 93(4): 1175 - 1183. [Abstract] [Full Text] [PDF]

				E. Carbone Ion Trafficking through T-type Ca2+ Channels: A Way to Look at Channel Gating Position J. Gen. Physiol., December 1, 2004; 124(6): 619 - 622. [Full Text] [PDF]

				C. A. Obejero-Paz, I. P. Gray, and S. W. Jones Y3+ Block Demonstrates an Intracellular Activation Gate for the {alpha}1G T-type Ca2+ Channel J. Gen. Physiol., November 29, 2004; 124(6): 631 - 640. [Abstract] [Full Text] [PDF]

				N. Leresche, J. Hering, and R. C. Lambert Paradoxical Potentiation of Neuronal T-Type Ca2+ Current by ATP at Resting Membrane Potential J. Neurosci., June 16, 2004; 24(24): 5592 - 5602. [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]

				K. Talavera, A. Janssens, N. Klugbauer, G. Droogmans, and B. Nilius Pore Structure Influences Gating Properties of the T-type Ca2+ Channel {alpha}1G J. Gen. Physiol., May 27, 2003; 121(6): 529 - 540. [Abstract] [Full Text] [PDF]

				K. Talavera, A. Janssens, N. Klugbauer, G. Droogmans, and B. Nilius Extracellular Ca2+ Modulates the Effects of Protons on Gating and Conduction Properties of the T-type Ca2+ Channel {alpha}1G (CaV3.1) J. Gen. Physiol., May 27, 2003; 121(6): 511 - 528. [Abstract] [Full Text] [PDF]

				K. Talavera, M. Staes, A. Janssens, N. Klugbauer, G. Droogmans, F. Hofmann, and B. Nilius Aspartate Residues of the Glu-Glu-Asp-Asp (EEDD) Pore Locus Control Selectivity and Permeation of the T-type Ca2+ Channel alpha 1G J. Biol. Chem., November 30, 2001; 276(49): 45628 - 45635. [Abstract] [Full Text] [PDF]