Biophys J, March 2001, p. 1238-1250, Vol. 80, No. 3

Alternatively Spliced _1G (Ca_V3.1) Intracellular Loops Promote Specific T-Type Ca²⁺ Channel Gating Properties

Institut de Génétique Humaine-CNRS UPR 1142-141, F-34396 Montpellier, France

At least three genes encode T-type calcium channel ₁ subunits, and identification of cDNA transcripts provided evidence that molecular diversity of these channels can be further enhanced by alternative splicing mechanisms, especially for the _1G subunit (Ca_V3.1). Using whole-cell patch-clamp procedures, we have investigated the electrophysiological properties of five isoforms of the human _1G subunit that display a distinct III-IV linker, namely, _1G-a, _1G-b, and _1G-bc, as well as a distinct II-III linker, namely, _1G-ae, _1G-be, as expressed in HEK-293 cells. We report that insertion e within the II-III linker specifically modulates inactivation, steady-state kinetics, and modestly recovery from inactivation, whereas alternative splicing within the III-IV linker affects preferentially kinetics and voltage dependence of activation, as well as deactivation and inactivation. By using voltage-clamp protocols mimicking neuronal activities, such as cerebellar train of action potentials and thalamic low-threshold spike, we describe that inactivation properties of _1G-a and _1G-ae isoforms can support channel behaviors reminiscent to those described in native neurons. Altogether, these data demonstrate that expression of distinct variants for the T-type _1G subunit can account for specific low-voltage-activated currents observed in neuronal tissues.

Biophys J, March 2001, p. 1238-1250, Vol. 80, No. 3
© 2001 by the Biophysical Society   0006-3495/01/03/1238/13  $2.00

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