Depletion of SK1 channel subunits leads to constitutive insulin secretion.
In the pancreas, the role of the small-conductance, calcium-activated SK channels remains controversial. Here, we show that three SK subtypes are expressed in the rat insulinoma cells. Our findings demonstrate that rat SK1 (rSK1) channels ensure appropriate insulin secretion by establishing the cell's negative resting membrane potential and shortening the duration of the action potential. We also found that the depletion of rSK1 transcripts generated a condition in which beta cells constitutively secrete insulin, even in the absence of a stimulating molecule (such as glucose). Together, these results implicate SK1 subunits as key regulators of excitability and endocrine function in beta cells.
Andres
Marilou A
MA
Pacific Biosciences Research Center, University of Hawaii, 1993 East-West Road, Honolulu, HI 96822, United States. marilou@pbrc.hawaii.edu
Baptista
Nicholas C
NC
Efird
Jimmy T
JT
Ogata
Kathleen K
KK
Bellinger
Frederick P
FP
Zeyda
Thomas
T
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D045744:Cell Line, Tumor; D006946:Hyperinsulinism / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D051381:Rats; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects
D007328:Insulin; C496896:Kcnn1 protein, rat; D021122:Protein Subunits; D051640:Small-Conductance Calcium-Activated Potassium Channels; D001030:Apamin