Electrophysiology of pancreatic A-, B- and D-cells studied in intact mouse islets of Langerhans

Research output: ThesisDoctoral Thesis (compilation)

Standard

Electrophysiology of pancreatic A-, B- and D-cells studied in intact mouse islets of Langerhans. / Göpel, Sven.

Molecular and Cellular Physiology, Lund University, 2001. 100 p.

Research output: ThesisDoctoral Thesis (compilation)

Harvard

Göpel, S 2001, 'Electrophysiology of pancreatic A-, B- and D-cells studied in intact mouse islets of Langerhans', Doctor, Department of Experimental Medical Science.

APA

Göpel, S. (2001). Electrophysiology of pancreatic A-, B- and D-cells studied in intact mouse islets of Langerhans. Molecular and Cellular Physiology, Lund University.

CBE

Göpel S. 2001. Electrophysiology of pancreatic A-, B- and D-cells studied in intact mouse islets of Langerhans. Molecular and Cellular Physiology, Lund University. 100 p.

MLA

Göpel, Sven Electrophysiology of pancreatic A-, B- and D-cells studied in intact mouse islets of Langerhans Molecular and Cellular Physiology, Lund University. 2001.

Vancouver

Göpel S. Electrophysiology of pancreatic A-, B- and D-cells studied in intact mouse islets of Langerhans. Molecular and Cellular Physiology, Lund University, 2001. 100 p.

Author

Göpel, Sven. / Electrophysiology of pancreatic A-, B- and D-cells studied in intact mouse islets of Langerhans. Molecular and Cellular Physiology, Lund University, 2001. 100 p.

RIS

TY - THES

T1 - Electrophysiology of pancreatic A-, B- and D-cells studied in intact mouse islets of Langerhans

AU - Göpel, Sven

N1 - Defence details Date: 2001-04-12 Time: 10:15 Place: Segerfalksalen, Wallenberg Neurocenter External reviewer(s) Name: Satin, Les Title: [unknown] Affiliation: [unknown] ---

PY - 2001

Y1 - 2001

N2 - Abstract The electrophysiological properties of insulin-secreting b-cells, glucagon-releasing a-cells and somatostation-producing d-cells in intact mouse pancreatic islets were investigated using the perforated patch whole-cell technique. It is demonstrated that it is possible to functionally identify the different cell types in situ. The ?-cells have a cell capacitance of 7.4 pF and differ from the ?- and ?-cells in lacking TTX-sensitive Na+-channels. Patch-clamp analysis of ?-cells in intact islets was applied to explain the grouping of action potentials to bursts in b-cells exposed to intermediate glucose concentrations. Electrical stimulation resulted in the gradual development of an outward K+-current, which deactivated slowly upon cessation of stimulation with a time course broadly consistent with a role in bursting (Kslow-current). A similar current was seen in isolated ?-cells but the amplitude was reduced by >80%, possibly explaining the lack of bursting in these cells. Inhibition of Ca2+-influx abolished the Kslow- current but it was resistant to apamin and charybdotoxin, two blockers of Ca2+-activated K+-channels. Ca2+-entry may instead lead to activation of ATP-regulated K+-channels by accelerated ATP-consumption as suggested by the observation that the Kslow-current was partially blocked by tolbutamide. The ?-cells are smaller than ?-cells as witnessed by a lower value of the cell capacitance (4.4 pF). They contain an L-type Ca2+-current, a TTX-sensitive Na+-current and a delayed outward K+-current. They also contained KATP-channels but the channel density was <50% of that seen in ?-cells. Glucagon-secreting ?-cells were occasionally seen to generate overshooting action potentials in the absence of glucose. An increased glucose concentration (to inhibit glucagon release) suppressed electrical activity but the membrane potential was paradoxically more depolarised than in the absence of the sugar. The size of the ?-cells was comparable to that of the ?-cell (5 pF) and like the ?-cells they contained a Na+-current that remained activatable at physiological membrane potentials. However, the steady-state inactivation of the Na+-current in the ?-cells occurred at voltages 20 mV more negative than seen in ?-cells (-47 mV instead of –28 mV). The a-cells are equipped with KATP-channels but the density was only »15% of that in the ?-cell. It is proposed that glucose inhibits glucagon release by closing KATP-channels. The associated depolarization leads to inactivation of the Na+- and T-type Ca2+-channels culminating in suppression of ?-cell electrical activity and glucagon release.

AB - Abstract The electrophysiological properties of insulin-secreting b-cells, glucagon-releasing a-cells and somatostation-producing d-cells in intact mouse pancreatic islets were investigated using the perforated patch whole-cell technique. It is demonstrated that it is possible to functionally identify the different cell types in situ. The ?-cells have a cell capacitance of 7.4 pF and differ from the ?- and ?-cells in lacking TTX-sensitive Na+-channels. Patch-clamp analysis of ?-cells in intact islets was applied to explain the grouping of action potentials to bursts in b-cells exposed to intermediate glucose concentrations. Electrical stimulation resulted in the gradual development of an outward K+-current, which deactivated slowly upon cessation of stimulation with a time course broadly consistent with a role in bursting (Kslow-current). A similar current was seen in isolated ?-cells but the amplitude was reduced by >80%, possibly explaining the lack of bursting in these cells. Inhibition of Ca2+-influx abolished the Kslow- current but it was resistant to apamin and charybdotoxin, two blockers of Ca2+-activated K+-channels. Ca2+-entry may instead lead to activation of ATP-regulated K+-channels by accelerated ATP-consumption as suggested by the observation that the Kslow-current was partially blocked by tolbutamide. The ?-cells are smaller than ?-cells as witnessed by a lower value of the cell capacitance (4.4 pF). They contain an L-type Ca2+-current, a TTX-sensitive Na+-current and a delayed outward K+-current. They also contained KATP-channels but the channel density was <50% of that seen in ?-cells. Glucagon-secreting ?-cells were occasionally seen to generate overshooting action potentials in the absence of glucose. An increased glucose concentration (to inhibit glucagon release) suppressed electrical activity but the membrane potential was paradoxically more depolarised than in the absence of the sugar. The size of the ?-cells was comparable to that of the ?-cell (5 pF) and like the ?-cells they contained a Na+-current that remained activatable at physiological membrane potentials. However, the steady-state inactivation of the Na+-current in the ?-cells occurred at voltages 20 mV more negative than seen in ?-cells (-47 mV instead of –28 mV). The a-cells are equipped with KATP-channels but the density was only »15% of that in the ?-cell. It is proposed that glucose inhibits glucagon release by closing KATP-channels. The associated depolarization leads to inactivation of the Na+- and T-type Ca2+-channels culminating in suppression of ?-cell electrical activity and glucagon release.

KW - somatostatin

KW - glucagon

KW - insulin

KW - patch-clamp

KW - membrane potential

KW - Pancreatic islet

KW - ion channel

KW - diabetes

KW - Physiology

KW - Fysiologi

M3 - Doctoral Thesis (compilation)

SN - 91-628-4686-8

PB - Molecular and Cellular Physiology, Lund University

ER -