We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Characterization of voltage-dependent Ca2+ channels in beta-cell line.
- Authors
Keahey, H H; Rajan, A S; Boyd, A E 3rd; Kunze, D L
- Abstract
Although there is compelling pharmacological evidence based on Ca2+-channel antagonist studies suggesting that the voltage-dependent Ca2+ channels regulate insulin release, no direct comparison with Ca2+ currents exists. This is particularly important because of the recent demonstration in other cell types of one and possibly two Ca2+ channels that are insensitive to Ca2+-channel antagonists, the dihydropyridines and the phenylalkylamines. Using an SV40-transformed pancreatic beta-cell line (HIT cells), we determined how voltage-dependent Ca2+ channels are involved in stimulus-secretion coupling. Ca2+ currents were measured with the tight-seal technique for whole-cell recording. The cytosolic free-Ca2+ concentration ([Ca2+]i) was followed with the fluorescent probe Fura 2, and the measurements were compared with insulin secretion stimulated by depolarizing the cells with K+. The Ca2+ current contained two components: a rapidly decaying current activated at -50 to -40 mV that decayed with a time constant of 25 ms and a very slowly decaying component activated at -40 mV. Both components were sensitive to the Ca2+-channel antagonist nimodipine. There is excellent agreement in the concentration of nimodipine that inhibited Ca2+ and the increase in [Ca2+]i in response to K+ depolarization (IC50 of 15 and 6 nM, respectively). Nimodipine inhibited insulin release over a similar dose-response range with an IC50 of 1.5 x 10(-9) M. These studies indicate that the increase in [Ca2+]i in response to beta-cell depolarization can be accounted for by the influx of this ion through a single class of dihydropyridine-sensitive Ca2+ channels in the cell membrane.
- Subjects
CALCIUM metabolism; ANIMAL experimentation; BARIUM; BIOLOGICAL transport; CALCIUM; CELL lines; COMPARATIVE studies; HETEROCYCLIC compounds; INSULIN; ISLANDS of Langerhans; RESEARCH methodology; MEDICAL cooperation; NIMODIPINE; POTASSIUM; RESEARCH; RESEARCH funding; EVALUATION research; PHARMACODYNAMICS
- Publication
Diabetes, 1989, Vol 38, Issue 2, p188
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.38.2.188