RGD Reference Report - Modulation of Kv2.1 channel gating and TEA sensitivity by distinct domains of SNAP-25. - Rat Genome Database

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Modulation of Kv2.1 channel gating and TEA sensitivity by distinct domains of SNAP-25.

Authors: He, Y  Kang, Y  Leung, YM  Xia, F  Gao, X  Xie, H  Gaisano, HY  Tsushima, RG 
Citation: He Y, etal., Biochem J. 2006 Jun 1;396(2):363-9.
RGD ID: 1581072
Pubmed: PMID:16478442   (View Abstract at PubMed)
PMCID: PMC1462716   (View Article at PubMed Central)
DOI: DOI:10.1042/BJ20051478   (Journal Full-text)

Distinct domains within the SNARE (soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor) proteins, STX1A (syntaxin 1A) and SNAP-25 (synaptosome-associated protein-25 kDa), regulate hormone secretion by their actions on the cell's exocytotic machinery, as well as voltage-gated Ca2+ and K+ channels. We examined the action of distinct domains within SNAP-25 on Kv2.1 (voltage gated K+ 2.1) channel gating. Dialysis of N-terminal SNAP-25 domains, S197 (SNAP-25(1-197)) and S180 (SNAP-25(1-180)), but not S206 (full-length SNAP-25(1-206)) increased the rate of Kv2.1 channel activation and slowed channel inactivation. Remarkably, these N-terminal SNAP-25 domains, acting on the Kv2.1 cytoplasmic N-terminus, potentiated the external TEA (tetraethylammonium)-mediated block of Kv2.1. To further examine whether these are effects of the channel pore domain, internal K+ was replaced with Na+ and external K+ was decreased from 4 to 1 mM, which decreased the IC50 of the TEA block from 6.8+/-0.9 mM to >100 mM. Under these conditions S180 completely restored TEA sensitivity (7.9+/-1.5 mM). SNAP-25 C-terminal domains, SNAP-25(198-206) and SNAP-25(181-197), had no effect on Kv2.1 gating kinetics. We conclude that different domains within SNAP-25 can form distinct complexes with Kv2.1 to execute a fine allosteric regulation of channel gating and the architecture of the outer pore structure in order to modulate cell excitability.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
voltage-gated potassium channel complex  IDA 1581072 RGD 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Kcnb1  (potassium voltage-gated channel subfamily B member 1)
Snap25  (synaptosome associated protein 25)


Additional Information