Dickerson, Matthew T. and Dadi, Prasanna K. and Altman, Molly K. and Verlage, Kenneth R. and Thorson, Ariel S. and Jordan, Kelli L. and Vierra, Nicholas C. and Amarnath, Gautami and Jacobson, David A. (2019) Glucose-mediated inhibition of calcium-activated potassium channels limits alpha-cell calcium influx and glucagon secretion. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 316 (4). E646-E659. ISSN 0193-1849, 1522-1555
Full text not available from this repository. (Request a copy)Abstract
Pancreatic alpha-cells exhibit oscillations in cytosolic Ca2+ (Ca-c(2+)), which control pulsatile glucagon (GCG) secretion. However, the mechanisms that modulate alpha-cell Ca-c(2+) oscillations have not been elucidated. As beta-cell Ca-c(2-) oscillations are regulated in part by Ca2+-activated K+(K-SLOW) currents, this work investigated the role of K-SLOW, in alpha-cell Ca(2+ )handling and GCG secretion. alpha-Cells displayed K-SLOW, currents that were dependent on Ca2+ influx through L- and P/Q-type voltage-dependent Ca2+ channels (VDCCs) as well as Ca2+ released from endoplasmic reticulum stores. a-Cell K s i m ., was decreased by small-conductance Ca'activated K+ (SK) channel inhibitors apamin and UCL 1684. largeconductance Ca2+-activated K+ (BK) channel inhibitor iberiotoxin (IbTx), and intermediate-conductance Ca2+-activated K+ (BK) channel inhibitor TRAM 34. Moreover, partial inhibition of alpha-cell K-SLOW, with apamin depolarized membrane potential (V-m) (3.8 +/- 0.7 mV) and reduced action potential (AP) amplitude (10.4 +/- 1.9 mV). Although apamin transiently increased Ca2+ influx into a-cells at low glucose (42.9 +/- 10.6%), sustained SK (38.5 +/- 10.4%) or BK channel inhibition (31.0 +/- 11.7%) decreased alpha-cell Ca2+ influx. Total alpha-cell Ca-c(2+) was similarly reduced (28.3 +/- 11.1%) following prolonged treatment with high glucose, but it was not decreased further by SK or BK channel inhibition. Consistent with reduced alpha-cell Ca-c(2+) following prolonged K-SLOW, inhibition. apamin decreased GCG secretion from mouse (20.4 +/- 4.2%) and human (27.7 +/- 13.1%) islets at low glucose. These data demonstrate that K-SLOW, activation provides a hyperpolarizing influence on alpha-cell V-m that sustains Ca2+ entry during hypoglycemic conditions, presumably by preventing voltage-dependent inactivation of P/Q-type VDCCs. Thus, when alpha-cell Ca-c(2+) is elevated during secretagogue stimulation, K-SLOW activation helps to preserve GCG secretion.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PANCREATIC BETA-CELLS; K-ATP CHANNELS; ENDOPLASMIC-RETICULUM; CA2+ CONCENTRATION; DELTA-CELLS; INSULIN; SOMATOSTATIN; RELEASE; GENERATION; CONTRIBUTE; alpha-cell; calcium handling; glucagon secretion; potassium channel |
| Subjects: | 100 Philosophy & psychology > 150 Psychology |
| Divisions: | Human Sciences > Institut für Psychologie > Lehrstuhl für Klinische Psychologie und Psychotherapie - Lehrstuhl für Psychologie VIII - Prof. Dr. Andreas Mühlberger |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Apr 2020 05:00 |
| Last Modified: | 21 Apr 2020 08:58 |
| URI: | https://pred.uni-regensburg.de/id/eprint/27259 |
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