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Permeation and Gating in Ca_V3.1 (1G) T-type Calcium Channels Effects of Ca²⁺, Ba²⁺, Mg²⁺, and Na⁺

Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106

Correspondence to Stephen W. Jones: swj{at}case.edu

We examined the concentration dependence of currents through Ca_V3.1 T-type calcium channels, varying Ca²⁺ and Ba²⁺ over a wide concentration range (100 nM to 110 mM) while recording whole-cell currents over a wide voltage range from channels stably expressed in HEK 293 cells. To isolate effects on permeation, instantaneous current–voltage relationships (IIV) were obtained following strong, brief depolarizations to activate channels with minimal inactivation. Reversal potentials were described by P_Ca/P_Na = 87 and P_Ca/P_Ba = 2, based on Goldman-Hodgkin-Katz theory. However, analysis of chord conductances found that apparent K_d values were similar for Ca²⁺ and Ba²⁺, both for block of currents carried by Na⁺ (3 µM for Ca²⁺ vs. 4 µM for Ba²⁺, at –30 mV; weaker at more positive or negative voltages) and for permeation (3.3 mM for Ca²⁺ vs. 2.5 mM for Ba²⁺; nearly voltage independent). Block by 3–10 µM Ca²⁺ was time dependent, described by bimolecular kinetics with binding at 3 x 10⁸ M^–1s^–1 and voltage-dependent exit. Ca²⁺_o, Ba²⁺_o, and Mg²⁺_o also affected channel gating, primarily by shifting channel activation, consistent with screening a surface charge of 1 e^– per 98 Ų from Gouy-Chapman theory. Additionally, inward currents inactivated 35% faster in Ba²⁺_o (vs. Ca²⁺_o or Na⁺_o). The accelerated inactivation in Ba²⁺_o correlated with the transition from Na⁺ to Ba²⁺ permeation, suggesting that Ba²⁺_o speeds inactivation by occupying the pore. We conclude that the selectivity of the "surface charge" among divalent cations differs between calcium channel families, implying that the surface charge is channel specific. Voltage strongly affects the concentration dependence of block, but not of permeation, for Ca²⁺ or Ba²⁺.

Abbreviations used in this article: GHK, Goldman-Hodgkin-Katz; HVA, high voltage–activated; IIV, instantaneous I-V; P_O,r, relative open probability; _IIV, time constant from IIV protocol; _Inact, time constant for inactivation; T_Peak, time-to-peak; V_1/2, voltage for half-maximal activation; V_R, reversal potential.

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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]

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