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J Biol Chem. 2014 Apr 25;289(17):11952-69. doi: 10.1074/jbc.M114.551473. Epub 2014 Mar 4.

T-type channels become highly permeable to sodium ions using an alternative extracellular turret region (S5-P) outside the selectivity filter.

Author information

  • 1From the Department of Biology, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.

Abstract

T-type (Cav3) channels are categorized as calcium channels, but invertebrate ones can be highly sodium-selective channels. We illustrate that the snail LCav3 T-type channel becomes highly sodium-permeable through exon splicing of an extracellular turret and descending helix in domain II of the four-domain Cav3 channel. Highly sodium-permeable T-type channels are generated without altering the invariant ring of charged residues in the selectivity filter that governs calcium selectivity in calcium channels. The highly sodium-permeant T-type channel expresses in the brain and is the only splice isoform expressed in the snail heart. This unique splicing of turret residues offers T-type channels a capacity to serve as a pacemaking sodium current in the primitive heart and brain in lieu of Nav1-type sodium channels and to substitute for voltage-gated sodium channels lacking in many invertebrates. T-type channels would also contribute substantially to sodium leak conductances at rest in invertebrates because of their large window currents.

KEYWORDS:

Alternative Splicing; Calcium Channels; Heart; Patch Clamp Electrophysiology; Permeability; Sodium Channels

PMID:
24596098
[PubMed - indexed for MEDLINE]
PMCID:
PMC4002102
[Available on 2015/4/25]

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