Ion channels involved in insulin release are activated by osmotic swelling of pancreatic B-cells.
Measurements of the membrane potential showed that osmotic swelling (-80 mosmol/l) of pancreatic B-cells led to a transient hyperpolarization followed by a more sustained depolarization of the cell membrane. Cell swelling triggers a transient activation of the K+ATP current and of an inward current, carried by Cl-. This current was inhibited by DIDS, D600, and by omission of extracellular Ca2+. The depolarization opens voltage dependent L-type Ca2+ channels, thereby increasing the intracellular Ca2+ activity ([Ca2+]i). This effect was blunted by D600 or abolished by omission of Ca2+. Moreover, osmotic swelling transiently increased the amplitude of the Ca2+ currents. Replacement of NaCl by d-mannitol proved that the observed effects are due to an increase in cell volume and not to a reduction of extracellular Na+ or Cl-. Our results suggest that regulatory volume decrease is achieved by activation of K+ and Cl- currents. The Cl- current is responsible for the previously described depolarization and increase in insulin release induced by osmotic cell swelling.
Drews
G
G
Institute of Physiology, Gmelinstr. 5, University of Tübingen, D-72076 Tübingen, FRG. Gisela.Drews@uni-tuebingen.de
Zempel
G
G
Krippeit-Drews
P
P
Britsch
S
S
Busch
G L
GL
Kaba
N K
NK
Lang
F
F
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D015220:Calcium Channels / Q000502:physiology; D018118:Chloride Channels / Q000378:metabolism; D005260:Female; D007328:Insulin / Q000378:metabolism*; D007424:Intracellular Fluid / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism* / Q000502:physiology; D007515:Islets of Langerhans / Q000378:metabolism* / Q000502:physiology*; D008564:Membrane Potentials; D051379:Mice; D008815:Mice, Inbred Strains; D009997:Osmotic Pressure; D015221:Potassium Channels / Q000502:physiology
D015220:Calcium Channels; D018118:Chloride Channels; D007328:Insulin; D007473:Ion Channels; D015221:Potassium Channels; D000255:Adenosine Triphosphate