title: Non-conducting function of the Kv2.1 channel enables it to recruit vesicles for release in neuroendocrine and nerve cells.
abstract: Regulation of exocytosis by voltage-gated K(+) channels has classically been viewed as inhibition mediated by K(+) fluxes. We recently identified a new role for Kv2.1 in facilitating vesicle release from neuroendocrine cells, which is independent of K(+) flux. Here, we show that Kv2.1-induced facilitation of release is not restricted to neuroendocrine cells, but also occurs in the somatic-vesicle release from dorsal-root-ganglion neurons and is mediated by direct association of Kv2.1 with syntaxin. We further show in adrenal chromaffin cells that facilitation induced by both wild-type and non-conducting mutant Kv2.1 channels in response to long stimulation persists during successive stimulation, and can be attributed to an increased number of exocytotic events and not to changes in single-spike kinetics. Moreover, rigorous analysis of the pools of released vesicles reveals that Kv2.1 enhances the rate of vesicle recruitment during stimulation with high Ca(2+), without affecting the size of the readily releasable vesicle pool. These findings place a voltage-gated K(+) channel among the syntaxin-binding proteins that directly regulate pre-fusion steps in exocytosis.
authors.affiliation: Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, 69978 Tel Aviv, Israel.
authors.forename: Lori
authors.initials: L
authors.lastname: Feinshreiber
authors.forename: Dafna
authors.initials: D
authors.lastname: Singer-Lahat
authors.forename: Reut
authors.initials: R
authors.lastname: Friedrich
authors.forename: Ulf
authors.initials: U
authors.lastname: Matti
authors.forename: Anton
authors.initials: A
authors.lastname: Sheinin
authors.forename: Ofer
authors.initials: O
authors.lastname: Yizhar
authors.forename: Rachel
authors.initials: R
authors.lastname: Nachman
authors.forename: Dodo
authors.initials: D
authors.lastname: Chikvashvili
authors.forename: Jens
authors.initials: J
authors.lastname: Rettig
authors.forename: Uri
authors.initials: U
authors.lastname: Ashery
authors.forename: Ilana
authors.initials: I
authors.lastname: Lotan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D020013:Calcium Signaling; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000378:metabolism* / Q000473:pathology; D004594:Electrophysiology; D005089:Exocytosis; D005727:Ganglia, Spinal / Q000473:pathology*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D050765:Qa-SNARE Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D022142:Secretory Vesicles / Q000378:metabolism*; D051669:Shab Potassium Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D050765:Qa-SNARE Proteins; D051669:Shab Potassium Channels