Distinct modulation of Kv1.2 channel gating by wild type, but not open form, of syntaxin-1A

SNARE proteins, syntaxin-1A (Syn-1A) and SNAP-25, inhibit delayed rectifier K+ channels, Kv1.1 and Kv2.1, in secretory cells. We showed previously that the mutant open conformation of Syn-1A (Syn-1A L165A/E166A) inhibits Kv2.1 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 Kv1.2, 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 Kv1.2 current magnitude. Of interest, wild-type Syn-1A caused a right shift in the activation curves of Kv1.2 without affecting its steady-state availability, an inhibition profile opposite to its effects on Kv2.1 (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 Kv1.2 in an expression system, open-form Syn-1A ...