Perchlorate stimulates insulin secretion by shifting the gating of L-type Ca2+ currents in mouse pancreatic B-cells towards negative potentials.
The effects of the chaotrophic anion perchlorate (ClO4-) on glucose-induced electrical activity, exocytosis and ion channel activity in mouse pancreatic B-cells were investigated by patch-clamp recordings and capacitance measurements. ClO4- stimulated glucose-induced electrical activity and increase...
| Main Authors: | , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2001
|
| _version_ | 1797069607220019200 |
|---|---|
| author | Larsson-Nyrén, G Sehlin, J Rorsman, P Renström, E |
| author_facet | Larsson-Nyrén, G Sehlin, J Rorsman, P Renström, E |
| author_sort | Larsson-Nyrén, G |
| collection | OXFORD |
| description | The effects of the chaotrophic anion perchlorate (ClO4-) on glucose-induced electrical activity, exocytosis and ion channel activity in mouse pancreatic B-cells were investigated by patch-clamp recordings and capacitance measurements. ClO4- 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. ClO4- did not influence ATP-dependent K (KATP) channel activity and voltage-gated delayed K+ current. Similarly, ClO4- had no effect on Ca2+-dependent exocytosis. The stimulation of electrical activity and insulin secretion was instead attributable to an enhancement of the whole-cell Ca2+ 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 Ca2+ current towards negative voltages. The action of ClO4- 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 ClO4- 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 ClO4- stimulates insulin secretion and electrical activity by exerting a BAY K8644-like action on Ca2+ channel gating. |
| first_indexed | 2024-03-06T22:26:58Z |
| format | Journal article |
| id | oxford-uuid:56fa4985-90a3-4004-8bab-af19fcaafaea |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:26:58Z |
| publishDate | 2001 |
| record_format | dspace |
| spelling | oxford-uuid:56fa4985-90a3-4004-8bab-af19fcaafaea2022-03-26T16:53:50ZPerchlorate stimulates insulin secretion by shifting the gating of L-type Ca2+ currents in mouse pancreatic B-cells towards negative potentials.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:56fa4985-90a3-4004-8bab-af19fcaafaeaEnglishSymplectic Elements at Oxford2001Larsson-Nyrén, GSehlin, JRorsman, PRenström, EThe effects of the chaotrophic anion perchlorate (ClO4-) on glucose-induced electrical activity, exocytosis and ion channel activity in mouse pancreatic B-cells were investigated by patch-clamp recordings and capacitance measurements. ClO4- 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. ClO4- did not influence ATP-dependent K (KATP) channel activity and voltage-gated delayed K+ current. Similarly, ClO4- had no effect on Ca2+-dependent exocytosis. The stimulation of electrical activity and insulin secretion was instead attributable to an enhancement of the whole-cell Ca2+ 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 Ca2+ current towards negative voltages. The action of ClO4- 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 ClO4- 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 ClO4- stimulates insulin secretion and electrical activity by exerting a BAY K8644-like action on Ca2+ channel gating. |
| spellingShingle | Larsson-Nyrén, G Sehlin, J Rorsman, P Renström, E Perchlorate stimulates insulin secretion by shifting the gating of L-type Ca2+ currents in mouse pancreatic B-cells towards negative potentials. |
| title | Perchlorate stimulates insulin secretion by shifting the gating of L-type Ca2+ currents in mouse pancreatic B-cells towards negative potentials. |
| title_full | Perchlorate stimulates insulin secretion by shifting the gating of L-type Ca2+ currents in mouse pancreatic B-cells towards negative potentials. |
| title_fullStr | Perchlorate stimulates insulin secretion by shifting the gating of L-type Ca2+ currents in mouse pancreatic B-cells towards negative potentials. |
| title_full_unstemmed | Perchlorate stimulates insulin secretion by shifting the gating of L-type Ca2+ currents in mouse pancreatic B-cells towards negative potentials. |
| title_short | Perchlorate stimulates insulin secretion by shifting the gating of L-type Ca2+ currents in mouse pancreatic B-cells towards negative potentials. |
| title_sort | perchlorate stimulates insulin secretion by shifting the gating of l type ca2 currents in mouse pancreatic b cells towards negative potentials |
| work_keys_str_mv | AT larssonnyreng perchloratestimulatesinsulinsecretionbyshiftingthegatingofltypeca2currentsinmousepancreaticbcellstowardsnegativepotentials AT sehlinj perchloratestimulatesinsulinsecretionbyshiftingthegatingofltypeca2currentsinmousepancreaticbcellstowardsnegativepotentials AT rorsmanp perchloratestimulatesinsulinsecretionbyshiftingthegatingofltypeca2currentsinmousepancreaticbcellstowardsnegativepotentials AT renstrome perchloratestimulatesinsulinsecretionbyshiftingthegatingofltypeca2currentsinmousepancreaticbcellstowardsnegativepotentials |