Patch-clamp characterisation of somatostatin-secreting -cells in intact mouse pancreatic islets.
The perforated patch whole-cell configuration of the patch-clamp technique was applied to superficial cells in intact mouse pancreatic islets. Three types of electrical activity were observed corresponding to alpha-, beta- and delta-cells. The delta-cells were electrically active in the presence of glucose but lacked the oscillatory pattern seen in the beta-cells. By contrast, the alpha-cells were electrically silent at high glucose concentrations but action potentials could be elicited by removal of the sugar. Both alpha- and beta-cells contained transient voltage-activated K+ currents. In the delta-cells, the K+ currents activated above -20 mV and were completely blocked by TEA (20 mM). The alpha-cells differed from the delta-cells in possessing a TEA-resistant K+ current activating already at -40 mV. Immunocytochemistry revealed the presence of Kv3.4 channels in delta-cells and TEA-resistant Kv4.3 channels in alpha-cells. Thus the presence of a transient TEA-resistant current can be used to functionally separate the delta- and alpha-cells. A TTX-sensitive Na+ current developed in delta-cells during depolarisations beyond -30 mV and reached a peak amplitude of 350 pA. Steady-state inactivation of this current was half-maximal at -28 mV. The delta-cells were also equipped with a sustained Ca2+ current that activated above -30 mV and reached a peak of 60 pA when measured at 2.6 mM extracellular Ca2+. A tolbutamide-sensitive KATP channel conductance was observed in delta-cells exposed to glucose-free medium. Addition of tolbutamide (0.1 mM) depolarised the delta-cell and evoked electrical activity. We propose that the KATP channels in delta-cells serve the same function as in the beta-cell and couple an elevation of the blood glucose concentration to stimulation of hormone release.
Göpel
S O
SO
Department of Molecular and Cellular Physiology, Diabetes Research Unit, Institute of Physiological Sciences, Lund University, Solvegatan 19, S-223 62 Lund, Sweden.
Kanno
T
T
Barg
S
S
Rorsman
P
P
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D004553:Electric Conductivity; D004594:Electrophysiology; D006706:Homeostasis; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D007515:Islets of Langerhans / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D051672:Shal Potassium Channels; D051670:Shaw Potassium Channels; D015222:Sodium Channels / Q000502:physiology; D013004:Somatostatin / Q000378:metabolism*; D019864:Somatostatin-Secreting Cells / Q000378:metabolism / Q000502:physiology*
C115399:Kcnc4 protein, mouse; C497022:Kcnd3 protein, mouse; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051672:Shal Potassium Channels; D051670:Shaw Potassium Channels; D015222:Sodium Channels; D013004:Somatostatin; D000255:Adenosine Triphosphate