Alternative splicing within the I–II loop controls surface expression of T-type Cav3.1 calcium channels

Shcheglovitov, Aleksandr; Vitko, Iuliia; Bidaud, Isabelle; Baumgart, Joel P.; Navarro-Gonzalez, Manuel F.; Grayson, T. Hilton; Lory, Philippe; Hill, Caryl E.; Perez-Reyes, Edward

doi:10.1016/j.febslet.2008.10.013

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Volume 582, Issue 27 , Pages 3765-3770, 12 November 2008

Alternative splicing within the I–II loop controls surface expression of T-type Ca_v3.1 calcium channels

Edited by Maurice Montal

Aleksandr Shcheglovitov
- Department of Pharmacology, University of Virginia, Charlottesville, VA 2908, USA
- A.S., I.V., and I.B. contributed equally to this work.
Iuliia Vitko
- Department of Pharmacology, University of Virginia, Charlottesville, VA 2908, USA
- A.S., I.V., and I.B. contributed equally to this work.
Isabelle Bidaud
- CNRS, UMR 5203, Institut de Génomique fonctionnelle, Montpellier, France
- INSERM, U661, Montpellier, France
- Université Montpellier, 1 et 2, Montpellier, France
- A.S., I.V., and I.B. contributed equally to this work.
Joel P. Baumgart
- Neuroscience Graduate Program, University of Virginia, Charlottesville, VA 22908, USA
Manuel F. Navarro-Gonzalez
- Division of Neuroscience, John Curtin School of Medical Research, The Australian National University, Canberra, Australia
T. Hilton Grayson
- Division of Neuroscience, John Curtin School of Medical Research, The Australian National University, Canberra, Australia
Philippe Lory
- CNRS, UMR 5203, Institut de Génomique fonctionnelle, Montpellier, France
- INSERM, U661, Montpellier, France
- Université Montpellier, 1 et 2, Montpellier, France
Caryl E. Hill
- Division of Neuroscience, John Curtin School of Medical Research, The Australian National University, Canberra, Australia
Edward Perez-Reyes
- Department of Pharmacology, University of Virginia, Charlottesville, VA 2908, USA
- Neuroscience Graduate Program, University of Virginia, Charlottesville, VA 22908, USA
- Corresponding author. Address: Department of Pharmacology, University of Virginia, Charlottesville, VA 2908, USA.

Received 4 August 2008; received in revised form 3 October 2008; accepted 6 October 2008. published online 17 October 2008.

Abstract

Molecular diversity of T-type/Ca_v3 Ca²⁺ channels is created by expression of three genes and alternative splicing of those genes. Prompted by the important role of the I–II linker in gating and surface expression of Ca_v3 channels, we describe here the properties of a novel variant that partially deletes this loop. The variant is abundantly expressed in rat brain, even exceeding transcripts with the complete exon 8. Electrophysiological analysis of the Δ8b variant revealed enhanced current density compared to Ca_v3.1a, but similar gating. Luminometry experiments revealed an increase in the expression of Δ8b channels at the plasma membrane. We conclude that alternative splicing of Ca_v3 channels regulates surface expression and may underlie disease states in which T-channel current density is increased.

Keywords: Ion channel, T-type calcium channel, Gene splicing, Electrophysiology, Luminometry, Epilepsy