A role for Ca2+-sensitive nonselective cation channels in regulating the membrane potential of pancreatic beta-cells

Diabetes
C A Leech, J F Habener

Abstract

The incretin hormones, glucagon-like peptide 1 and pituitary adenylyl cyclase-activating polypeptide, are proposed to activate a maitotoxin (MTX)-sensitive, Ca2+-dependent nonselective cation current in pancreatic beta-cells and insulinoma cells. This MTX-sensitive current is present in human beta-cells as well as in mouse and rat beta-cells, and is accompanied by a rise in cytosolic Ca2+ in voltage-clamped cells in which the activation of voltage-dependent Ca2+ channels is prevented. Activation of the nonselective cation current is inhibited by reduction of disulfide bonds with intracellular, but not extracellular, dithiothreitol, and is also abolished by intracellular dialysis with trypsin. The nonselective cation channels that carry this current have a conductance of about 30 pS, with Na+ as the major extracellular cation. We estimate that these cation channels are expressed on beta-cells at a density similar to that of ATP-sensitive potassium channels (K(ATP) channels) and exhibit spontaneous activity at basal glucose concentrations. We propose that this spontaneous cation channel activity constitutes at least part of the depolarizing background conductance that permits changes in the activity of K(ATP) channels to regulate...Continue Reading

Citations

Nov 3, 2004·The Journal of Membrane Biology·David Mears
Feb 1, 2002·Toxicon : Official Journal of the International Society on Toxinology·V Morales-Tlalpan, L Vaca
Apr 4, 2000·Diabetic Medicine : a Journal of the British Diabetic Association·M J Dunne
Mar 3, 2010·Proceedings of the National Academy of Sciences of the United States of America·Barbara ColsoulRudi Vennekens
Jun 29, 2011·The Journal of General Physiology·Chae Young ChaAkinori Noma
Oct 13, 2009·Diabetes, Obesity & Metabolism·J C HenquinA Szollosi
Jul 16, 2010·American Journal of Physiology. Endocrinology and Metabolism·L E FridlyandL H Philipson
Jan 7, 2014·PLoS Computational Biology·Michela RizMorten Gram Pedersen
Jul 26, 2011·Progress in Biophysics and Molecular Biology·Colin A LeechGeorge G Holz
Aug 19, 2011·IEEE Transactions on Bio-medical Engineering·Morten Gram PedersenClaudio Cobelli
Apr 23, 2009·Biophysical Journal·L E FridlyandL H Philipson
Dec 12, 2002·Diabetes·Patrick E MacDonaldMichael B Wheeler
Jun 18, 2016·The FEBS Journal·Ji Liu, Zhiping P Pang
Aug 27, 2016·Diabetes, Obesity & Metabolism·Bo LiuShanta J Persaud
Apr 7, 2005·American Journal of Physiology. Endocrinology and Metabolism·R Cruz-CruzM Hiriart
Dec 22, 1999·Endocrine Reviews·T J Kieffer, J F Habener
Mar 7, 2002·American Journal of Physiology. Cell Physiology·Rosalba I FonterizJavier García-Sancho
Apr 25, 2000·The Journal of Biological Chemistry·N NakashimaJ M Olefsky
Oct 10, 2003·American Journal of Physiology. Endocrinology and Metabolism·Yoshikazu Miura, Hisao Matsui
Mar 20, 2003·American Journal of Physiology. Endocrinology and Metabolism·Leonid E FridlyandLouis H Philipson
Dec 31, 2002·Biochemical and Biophysical Research Communications·Frank ThévenodCatherine M Fuller
Sep 16, 2021·Journal of Diabetes Investigation·Shunsuke FunazakiKatsuya Dezaki

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adenoma, Islet Cell

Islet Cell Adenoma arises in the islet cells, which are insulin producing cells of the pancreas. These tumors can be either malignant or benign. Discover the latest research on Islet Cell Adenoma here.

American Diabetes Association Journals

Discover the latest diabetes research published by the journals from the American Diabetes Association.

Cardiovascular Biology of GLP-1

Glucagon-like peptide 1 (GLP-1) plays a role in glucose metabolism, energy homeostasis, and inflammation suppression. GLP-1 receptor signaling has been shown to impact cardiovascular function. This feed focuses on the role of GLP-1 and GLP-1 receptor agonists on cardiovascular biology.