Depletion of intracellular Ca2+ stores activates a maitotoxin-sensitive nonselective cationic current in beta-cells

• Published in: The Journal of biological chemistry 1994-12, Vol.269 (51), p.32055-32058
• Main Authors: J F Worley, 3rd, M S McIntyre, B Spencer, I D Dukes
• Format: Article
• Language: English
• Subjects: Animals; Calcium - metabolism; Calcium Channels - drug effects; Calcium Channels - physiology; In Vitro Techniques; Islets of Langerhans - drug effects; Islets of Langerhans - physiology; Marine Toxins - pharmacology; Membrane Potentials; Mice; Mice, Inbred C57BL; Oxocins
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(18)31599-0

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.