The 25-kDa synaptosome-associated protein (SNAP-25) binds and inhibits delayed rectifier potassium channels in secretory cells

Junzhi Ji, Sharon Tsuk, Anne Marie F. Salapatek, Xiaohang Huang, Dodo Chikvashvili, Ewa A. Pasyk, Youhou Kang, Laura Sheu, Robert Tsushima, Nicholas Diamant, William S. Trimble, Ilana Lotan, Herbert Y. Gaisano

Research output: Contribution to journalArticlepeer-review

Abstract

Delayed-rectifier K+ channels (KDR) are important regulators of membrane excitability in neurons and neuroendocrine cells. Opening of these voltage-dependent K+ channels results in membrane repolarization, leading to the closure of the Ca2+ channels and cessation of insulin secretion in neuroendocrine islet β cells. Using patch clamp techniques, we have demonstrated that the activity of the KDR channel subtype, Kv1.1, identified by its specific blocker dendrodotoxin-K, is inhibited by SNAP-25 in insulinoma HIT-T15 β cells. A coprecipitation study of rat brain confirmed that SNAP-25 interacts with the Kv1.1 protein. Cleavage of SNAP-25 by expression of botulinum neurotoxin A in HIT-T15 cells relieved this SNAP-25-mediated inhibition of KDR. This inhibitory effect of SNAP-25 is mediated by the N terminus of Kv1.1, likely by direct interactions with K1.1 and/or Kvβ subunits, as revealed by co-immunoprecipitation performed in the Xenopus oocyte expression system and in vitro binding. Taken together we have concluded that SNAP-25 mediates secretion not only through its participation in the exocytotic SNARE complex but also by regulating membrane potential and calcium entry through its interaction with KDR channels.

Original languageEnglish
Pages (from-to)20195-20204
Number of pages10
JournalJournal of Biological Chemistry
Volume277
Issue number23
DOIs
StatePublished - 7 Jun 2002
Externally publishedYes

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