Résumé
At least three genes encode T-type calcium channel
α
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
α
1G subunit (Ca
V3.1). Using whole-cell patch-clamp procedures, we have investigated the electrophysiological properties of five isoforms of the human
α
1G subunit that display a distinct III-IV linker, namely,
α
1G-a,
α
1G-b, and
α
1G-bc, as well as a distinct II-III linker, namely,
α
1G-ae,
α
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
α
1G-a and
α
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
α
1G subunit can account for specific low-voltage-activated currents observed in neuronal tissues.