Small-conductance calcium-activated K+ channels are expressed in pancreatic islets and regulate glucose responses

Diabetes. 2003 Aug;52(8):2000-6. doi: 10.2337/diabetes.52.8.2000.


Glucose-stimulated insulin secretion is associated with transients of intracellular Ca(2+) concentration [Ca(2+)](i) in the pancreatic beta-cell. We identified the expression and function of specific small-conductance Ca(2+)-activated K(+) (SK) channel genes in insulin-secreting cells. The presence of mRNA for SK1, -2, -3, and -4 (intermediate-conductance Ca(2+)-activated K(+) 1 [IK1]) channels was demonstrated by RT-PCR in rodent islets and insulinoma cells. SK2 and -3 proteins in mouse islets were detected by immunoblot and immunocytochemistry. In the tTA-SK3 tet-off mouse, a normal amount of SK3 protein was present in islets, but it became undetectable after exposure to doxycycline (DOX), which inhibits the transcription of the tTA-SK3 gene. The SK/IK channel-blockers apamin, dequalinium, and charybdotoxin caused increases in average [Ca(2+)](i) levels and in frequency of [Ca(2+)](i) oscillations in wild-type mouse islets. In SK3-tTA tet-off mice, the addition of apamin with glucose and tetraethylammonium (TEA) caused a similar elevation in [Ca(2+)](i), which was greatly diminished after DOX suppression of SK3 expression. We conclude that SK1, -2, -3, and IK1 (SK4) are expressed in islet cells and insulin-secreting cells and are able to influence glucose-induced calcium responses, thereby regulating insulin secretion.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies
  • Apamin / pharmacology
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology
  • Cells, Cultured
  • Charybdotoxin / pharmacology
  • Dequalinium / pharmacology
  • Gene Expression / physiology
  • Glucose / metabolism*
  • Intermediate-Conductance Calcium-Activated Potassium Channels
  • Islets of Langerhans / cytology
  • Islets of Langerhans / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels / genetics*
  • Potassium Channels / immunology
  • Potassium Channels / metabolism*
  • Potassium Channels, Calcium-Activated*
  • Small-Conductance Calcium-Activated Potassium Channels
  • Tetraethylammonium / pharmacology


  • Antibodies
  • Intermediate-Conductance Calcium-Activated Potassium Channels
  • Kcnn1 protein, mouse
  • Kcnn2 protein, mouse
  • Kcnn3 protein, mouse
  • Kcnn4 protein, mouse
  • Potassium Channel Blockers
  • Potassium Channels
  • Potassium Channels, Calcium-Activated
  • Small-Conductance Calcium-Activated Potassium Channels
  • Charybdotoxin
  • Apamin
  • Tetraethylammonium
  • Dequalinium
  • Glucose