Alternatively Spliced α1G (CaV3.1) Intracellular Loops Promote Specific T-Type Ca2+ Channel Gating Properties

By J. Chemin, A. Monteil, E. Bourinet, J. Nargeot, P. Lory. 2001

120 citations recorded by the source corpus.

Abstract 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 V 3.1). 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.

Subfields: Cardiology and Cardiovascular Medicine, Cellular and Molecular Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/111f438a3df070bdf55b232c12798eada523e7b2

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cardiology and Cardiovascular Medicine

1. E. Perez-Reyes
2. G. Zamponi
3. J. Nerbonne
4. R. Kass

In Cellular and Molecular Neuroscience

1. E. Perez-Reyes
2. J. Chemin
3. J. Nargeot
4. P. Lory
5. G. Zamponi
6. J. Striessnig
7. R. Kass
8. J. Nerbonne

In Molecular Biology

1. E. Perez-Reyes
2. J. Chemin
3. J. Nargeot
4. P. Lory
5. G. Zamponi
6. J. Striessnig
7. J. Nerbonne
8. R. Kass

Citations in the corpus

• Neuronal T-type α1H Calcium Channels Induce Neuritogenesis and Expression of High-Voltage-Activated Calcium Channels in the NG108–15 Cell Line (2002, methodology): “The NG108–15 cell line was used between 15 and 40 passages and was cultured as described previously (Chemin et al., 2001b).”
• Specific contribution of human T‐type calcium channel isotypes (α1G, α1H and α1I) to neuronal excitability (2002, methodology): “It should be noted, however, that splice variations can tune the properties of each isotype (Chemin et al. 2001).”
• Molecular physiology of low-voltage-activated t-type calcium channels. (2003, background): “These variants differ in their electrophysiological properties (68) and may ac-”
• The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential (2015, background): “Anandamide and its derivative Na-Gly (arachidonyl glycine) mediate potent inhibition of CaV3 calcium channels (Chemin et al., 2001b; Barbara et al., 2009).”