Distinct modulation of Kv1.2 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; pp. G1233 - G1242
• Main Authors: Neshatian, Leila, Leung, Yuk M, Kang, Youhou, Gao, Xiaodong, Xie, Huanli, Tsushima, Robert G, Gaisano, Herbert Y, Diamant, Nicholas E
• Format: Journal Article
• Language: English
• Published: United States 01.05.2007
• Subjects: Animals; Cats; Cells, Cultured; Epithelial Cells - cytology; Epithelial Cells - drug effects; Epithelial Cells - physiology; Female; Humans; Ion Channel Gating - drug effects; Kv1.2 Potassium Channel - physiology; Male; Munc18 Proteins - biosynthesis; Muscle, Smooth - cytology; Muscle, Smooth - drug effects; Nerve Tissue Proteins - biosynthesis; Protein Conformation; Rats; Syntaxin 1 - pharmacology
• ISSN: 0193-1857; 1522-1547
• DOI: 10.1152/ajpgi.00473.2006

SNARE proteins, syntaxin-1A (Syn-1A) and SNAP-25, inhibit delayed rectifier K(+) channels, K(v)1.1 and K(v)2.1, in secretory cells. We showed previously that the mutant open conformation of Syn-1A (Syn-1A L165A/E166A) inhibits K(v)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 K(v)1.2, a major delayed rectifier K(+) channel in nonsecretory smooth muscle cells and some neuronal tissues. In coexpression and acute dialysis studies, wild-type Syn-1A inhibited K(v)1.2 current magnitude. Of interest, wild-type Syn-1A caused a right shift in the activation curves of K(v)1.2 without affecting its steady-state availability, an inhibition profile opposite to its effects on K(v)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 K(v)1.2 in an expression system, open-form Syn-1A failed to reduce K(v)1.2 current magnitude or affect its gating. This is in contrast to the reported more potent effect of open-form Syn-1A on K(v)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 K(v) channels by Syn-1A and is compatible with versatility of Syn-1A modulation of repolarization in various secretory and nonsecretory (smooth muscle) cell types.