This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints, Permissions and Rights Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Leung, Y. M. Articles by Gaisano, H. Y. Search for Related Content PubMed PubMed Citation Articles by Leung, Y. M. Articles by Gaisano, H. Y.

SNAREing Voltage-Gated K⁺ and ATP-Sensitive K⁺ Channels: Tuning ß-Cell Excitability with Syntaxin-1A and Other Exocytotic Proteins

Department of Physiology (Y.M.L.) and Graduate Institute of Neural and Cognitive Sciences (Y.M.L.), China Medical University, Taichung 40402, Taiwan; and Departments of Medicine and Physiology (E.P.K., B.N., Y.K., H.Y.G.), University of Toronto, Toronto, Canada M5S 2A8

Correspondence: Address all correspondence and requests for reprints to: Dr. Herbert Gaisano, Room 7226, Medical Sciences Building, University of Toronto, Toronto, Ontario, Canada M5S 2A8. E-mail: herbert.gaisano{at}utoronto.ca; or Dr. Yuk-Man Leung, Department of Physiology, China Medical University, Taichung 40402, Taiwan. E-mail: ymleung{at}mail.cmu.edu.tw

The three SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins, syntaxin, SNAP25 (synaptosome-associated protein of 25 kDa), and synaptobrevin, constitute the minimal machinery for exocytosis in secretory cells such as neurons and neuroendocrine cells by forming a series of complexes prior to and during vesicle fusion. It was subsequently found that these SNARE proteins not only participate in vesicle fusion, but also tether with voltage-dependent Ca²⁺ channels to form an excitosome that precisely regulates calcium entry at the site of exocytosis. In pancreatic islet ß-cells, ATP-sensitive K⁺ (K_ATP) channel closure by high ATP concentration leads to membrane depolarization, voltage-dependent Ca²⁺ channel opening, and insulin secretion, whereas subsequent opening of voltage-gated K⁺ (Kv) channels repolarizes the cell to terminate exocytosis. We have obtained evidence that syntaxin-1A physically interacts with Kv2.1 (the predominant Kv in ß-cells) and the sulfonylurea receptor subunit of ß-cell K_ATP channel to modify their gating behaviors. A model has proposed that the conformational changes of syntaxin-1A during exocytosis induce distinct functional modulations of K_ATP and Kv2.1 channels in a manner that optimally regulates cell excitability and insulin secretion. Other proteins involved in exocytosis, such as Munc-13, tomosyn, rab3a-interacting molecule, and guanyl nucleotide exchange factor II, have also been implicated in direct or indirect regulation of ß-cell ion channel activities and excitability. This review discusses this interesting aspect that exocytotic proteins not only promote secretion per se, but also fine-tune ß-cell excitability via modulation of ion channel gating.

This article has been cited by other articles:

				A. Honsbein, S. Sokolovski, C. Grefen, P. Campanoni, R. Pratelli, M. Paneque, Z. Chen, I. Johansson, and M. R. Blatt A Tripartite SNARE-K+ Channel Complex Mediates in Channel-Dependent K+ Nutrition in Arabidopsis PLANT CELL, September 1, 2009; 21(9): 2859 - 2877. [Abstract] [Full Text] [PDF]

				S. M. P. Jacobo, M. L. Guerra, R. E. Jarrard, J. A. Przybyla, G. Liu, V. J. Watts, and G. H. Hockerman The Intracellular II-III Loops of Cav1.2 and Cav1.3 Uncouple L-Type Voltage-Gated Ca2+ Channels from Glucagon-Like Peptide-1 Potentiation of Insulin Secretion in INS-1 Cells via Displacement from Lipid Rafts J. Pharmacol. Exp. Ther., July 1, 2009; 330(1): 283 - 293. [Abstract] [Full Text] [PDF]

				J. Zhang, R. Luo, H. Wu, S. Wei, W. Han, and G. Li Role of Type I{alpha} Phosphatidylinositol-4-Phosphate 5-Kinase in Insulin Secretion, Glucose Metabolism, and Membrane Potential in INS-1 {beta}-Cells Endocrinology, May 1, 2009; 150(5): 2127 - 2135. [Abstract] [Full Text] [PDF]

				B. Ng, Y. Kang, H. Xie, H. Sun, and H. Y. Gaisano Syntaxin-1A inhibition of P-1075, cromakalim, and diazoxide actions on mouse cardiac ATP-sensitive potassium channel Cardiovasc Res, December 1, 2008; 80(3): 365 - 374. [Abstract] [Full Text] [PDF]

				M. Prentki and S. R. M. Madiraju Glycerolipid Metabolism and Signaling in Health and Disease Endocr. Rev., October 1, 2008; 29(6): 647 - 676. [Abstract] [Full Text] [PDF]

				J. L. R. Williams, G. K. Fyfe, C. P. Sibley, P. N. Baker, and S. L. Greenwood K+ channel inhibition modulates the biochemical and morphological differentiation of human placental cytotrophoblast cells in vitro Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2008; 295(4): R1204 - R1213. [Abstract] [Full Text] [PDF]

				D. C. Bassham and M. R. Blatt SNAREs: Cogs and Coordinators in Signaling and Development Plant Physiology, August 1, 2008; 147(4): 1504 - 1515. [Full Text] [PDF]

				L. Eliasson, F. Abdulkader, M. Braun, J. Galvanovskis, M. B. Hoppa, and P. Rorsman Novel aspects of the molecular mechanisms controlling insulin secretion J. Physiol., July 15, 2008; 586(14): 3313 - 3324. [Abstract] [Full Text] [PDF]