Small-conductance calcium-activated K+ channels are expressed in pancreatic islets and regulate glucose responses.
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.
Tamarina
Natalia A
NA
Department of Medicine, University of Chicago, Chicago, Illinois, USA.
Wang
Yong
Y
Mariotto
Loris
L
Kuznetsov
Andrey
A
Bond
Chris
C
Adelman
John
J
Philipson
Louis H
LH
D000818:Animals; D000906:Antibodies; D001030:Apamin / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018999:Charybdotoxin / Q000494:pharmacology; D003868:Dequalinium / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels; D019789:Tetraethylammonium / Q000494:pharmacology
D000906:Antibodies; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496895:Kcnn1 protein, mouse; C496898:Kcnn2 protein, mouse; C496900:Kcnn3 protein, mouse; C496925:Kcnn4 protein, mouse; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels; D018999:Charybdotoxin; D001030:Apamin; D019789:Tetraethylammonium; D003868:Dequalinium; D005947:Glucose