Perchlorate stimulates insulin secretion by shifting the gating of L-type Ca super(2+) currents in mouse pancreatic B-cells towards negative potentials

• Published in: Pflügers Archiv Vol. 441; no. 5; pp. 587 - 595
• Main Authors: Larsson-Nyren, G, Sehlin, J, Rorsman, P, Renstroem, E
• Format: Journal Article
• Language: English
• Published: 01.01.2001
• Subjects: Perchlorate
• ISSN: 0031-6768
• DOI: 10.1007/s004240000426

The effects of the chaotrophic anion perchlorate (ClO sub(4) super(-)) on glucose-induced electrical activity, exocytosis and ion channel activity in mouse pancreatic B-cells were investigated by patch-clamp recordings and capacitance measurements. ClO sub(4) super(-) stimulated glucose-induced electrical activity and increased the action potential frequency by 70% whilst not affecting the membrane potential when applied in the presence of a subthreshold concentration of the sugar ClO sub(4) super(-) did not influence ATP-dependent K (K sub(ATP)) channel activity and voltage-gated delayed K super(+) current. Similarly, ClO sub(4) super(-) had no effect on Ca super(2+)-dependent exocytosis. The stimulation of electrical activity and insulin secretion was instead attributable to an enhancement of the whole-cell Ca super(2+) current. This effect was particularly pronounced at voltages around the threshold for action potential initiation and a doubling of the current amplitude was observed at -30 mV. This was due to a 7-mV shift in the gating of the Ca super(2+) current towards negative voltages. The action of ClO sub(4) super(-) was more pronounced when added in the presence of 0.1 mM BAY K8644, whereas no stimulation was observed when applied at a maximal concentration of the agonist (1 mM). Single-channel recordings revealed that the effect of ClO sub(4) super(-) on whole-cell currents was principally due to a 60% increase in the mean duration of the long openings and the number of active channels. We propose that ClO sub(4) super(-) stimulates insulin secretion and electrical activity by exerting a BAY K8644-like action on Ca super(2+) channel gating.