T-type Channels Become Highly Permeable to Sodium Ions Using an Alternate Extracellular Turret Region (S5-P) Outside the Selectivity Filter [Neurobiology]
March 4th, 2014 by Senatore, A., Guan, W., Boone, A. N., Spafford, J. D.
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 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.