Distinct modulation of K^sub v^1.2 channel gating by wild type, but not open form, of syntaxin-1A

• Published in: American journal of physiology: Gastrointestinal and liver physiology Vol. 292; no. 5; p. G1233
• Main Authors: Neshatian, Leila, Leung, Yuk M, Kang, Youhou, Gao, Xiaodong
• Format: Journal Article
• Language: English
• Published: Bethesda American Physiological Society 01.05.2007
• Subjects: Biochemistry; Cells; Excretory system; Ions; Proteins
• ISSN: 0193-1857; 1522-1547

SNARE proteins, syntaxin-1A (Syn-1A) and SNAP-25, inhibit delayed rectifier ... channels, ...1.1 and ...2.1, in secretory cells. We showed previously that the mutant open conformation of Syn-1A (Syn-1A L165A/E166A) inhibits ...2.1 channels more optimally than wild-type Syn-1A. In this report we examined whether Syn-1A in its wild-type and open conformations would exhibit similar differential actions on the gating of ...1.2, a maj or delayed rectifier ... channel in nonsecretory smooth muscle cells and some neuronal tissues. In coexpression and acute dialysis studies, wild-type Syn-1A inhibited ...1.2 current magnitude. Of interest, wild-type Syn-1A caused a right shift in the activation curves of ...1.2 without affecting its steady-state availability, an inhibition profile opposite to its effects on ...2.1 (steady-state availability reduction without changes in voltage dependence of activation). Also, although both wild-type and open-form Syn-1A bound equally well to ...1.2 in an expression system, open-form Syn-1A failed to reduce ...1.2 current magnitude or affect its gating. This is in contrast to the reported more potent effect of open-form Syn-1A on ...2.1 channels in secretory cells. This finding together with the absence of Munc18 and/or 13-1 in smooth muscles suggested that a change to an open conformation Syn-1A, normally facilitated by Munc18/13-1, is not required in nonsecretory smooth muscle cells. Taken together with previous reports, our results demonstrate the multiplicity of gating inhibition of different ... channels by Syn-1A and is compatible with versatility of Syn-1A modulation of repolarization in various secretory and nonsecretory (smooth muscle) cell types. (ProQuest-CSA LLC: ... denotes formulae/symbols omitted.)