A role for calcium release-activated current (CRAC) in cholinergic modulation of electrical activity in pancreatic beta-cells.
S. Bordin and colleagues have proposed that the depolarizing effects of acetylcholine and other muscarinic agonists on pancreatic beta-cells are mediated by a calcium release-activated current (CRAC). We support this hypothesis with additional data, and present a theoretical model which accounts for most known data on muscarinic effects. Additional phenomena, such as the biphasic responses of beta-cells to changes in glucose concentration and the depolarizing effects of the sarco-endoplasmic reticulum calcium ATPase pump poison thapsigargin, are also accounted for by our model. The ability of this single hypothesis, that CRAC is present in beta-cells, to explain so many phenomena motivates a more complete characterization of this current.
Bertram
R
R
Mathematical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Smolen
P
P
Sherman
A
A
Mears
D
D
Atwater
I
I
Martin
F
F
Soria
B
B
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002217:Carbachol / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology*; D004721:Endoplasmic Reticulum / Q000201:enzymology; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008433:Mathematics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D012519:Sarcoplasmic Reticulum / Q000201:enzymology; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D013997:Time Factors
D018678:Cholinergic Agents; D007328:Insulin; D013729:Terpenes; D019284:Thapsigargin; D002217:Carbachol; D000252:Calcium-Transporting ATPases; D005947:Glucose; D000109:Acetylcholine; D002118:Calcium