title: T-type channels become highly permeable to sodium ions using an alternative extracellular turret region (S5-P) outside the selectivity filter.
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.
authors.affiliation: Department of Biology, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.
authors.forename: Adriano
authors.initials: A
authors.lastname: Senatore
authors.affiliation: Department of Biology, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.
authors.forename: Wendy
authors.initials: W
authors.lastname: Guan
authors.affiliation: Department of Biology, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.
authors.forename: Adrienne N
authors.initials: AN
authors.lastname: Boone
authors.affiliation: Department of Biology, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada. Electronic address: spafford@uwaterloo.ca.
authors.forename: J David
authors.initials: JD
authors.lastname: Spafford
mesh_terms: D000818:Animals; D001483:Base Sequence; D020747:Calcium Channels, T-Type / Q000235:genetics / Q000378:metabolism*; D002412:Cations; D002478:Cells, Cultured; D003001:Cloning, Molecular; D017931:DNA Primers; D018408:Patch-Clamp Techniques; D010539:Permeability; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D012908:Snails; D012964:Sodium / Q000378:metabolism*
chemical_list: D020747:Calcium Channels, T-Type; D002412:Cations; D017931:DNA Primers; D012964:Sodium
keywords: Alternative Splicing; Calcium Channels; Heart; Patch Clamp Electrophysiology; Permeability; Sodium Channels