Non-conducting function of the Kv2.1 channel enables it to recruit vesicles for release in neuroendocrine and nerve cells.
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.
Feinshreiber
Lori
L
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, 69978 Tel Aviv, Israel.
Singer-Lahat
Dafna
D
Friedrich
Reut
R
Matti
Ulf
U
Sheinin
Anton
A
Yizhar
Ofer
O
Nachman
Rachel
R
Chikvashvili
Dodo
D
Rettig
Jens
J
Ashery
Uri
U
Lotan
Ilana
I
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*
D050765:Qa-SNARE Proteins; D051669:Shab Potassium Channels