Depletion of intracellular Ca2+ stores activates a maitotoxin-sensitive nonselective cationic current in beta-cells.
Glucose stimulation of beta-cell insulin secretion is initiated by membrane depolarization coupled with an elevation in intracellular Ca2+ concentration ([Ca2+]i). Both depolarization-dependent Ca2+ entry and intracellular Ca2+ store release contribute to the sugar-induced rise in [Ca2+]i. Here we show that maneuvers depleting intracellular Ca2+ stores induce membrane depolarization and a sustained nitrendipine-sensitive Ca2+ influx, whereas interventions promoting Ca2+ store refilling produce a hyperpolarization and inhibit Ca2+ influx. Both intracellular Ca2+ store depletion and maitotoxin activated a depolarizing nonselective cation current carried principally by Na+ in the physiological range of membrane potentials. The activation of such a current may form the paradigm by which excitable cells refill depleted intracellular Ca2+ stores by depolarization-driven opening of voltage-activated Ca2+ channels.
Worley
J F
JF
Department of Cell Physiology, Glaxo Research Institute, Research Triangle Park, North Carolina 27709.
McIntyre
M S
MS
Spencer
B
B
Dukes
I D
ID
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000187:drug effects* / Q000502:physiology; D008387:Marine Toxins / Q000494:pharmacology*; D008564:Membrane Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D035964:Oxocins; D000095702:Polyether Toxins
D002118:Calcium; D015220:Calcium Channels; D008387:Marine Toxins; D035964:Oxocins; C020394:maitotoxin; D000095702:Polyether Toxins