Depletion of SK1 channel subunits leads to constitutive insulin secretion

Andres, Marilou A.; Baptista, Nicholas C.; Efird, Jimmy T.; Ogata, Kathleen K.; Bellinger, Frederick P.; Zeyda, Thomas

doi:10.1016/j.febslet.2008.12.024

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Volume 583, Issue 2 , Pages 369-376, 22 January 2009

Depletion of SK1 channel subunits leads to constitutive insulin secretion

Edited by Aleksander Benjak

Marilou A. Andres
- Pacific Biosciences Research Center, University of Hawaii, 1993 East–West Road, Honolulu, HI 96822, United States
- Corresponding author. Fax: +1 808 956 6984.
Nicholas C. Baptista
- Pacific Biosciences Research Center, University of Hawaii, 1993 East–West Road, Honolulu, HI 96822, United States
Jimmy T. Efird
- Pacific Biosciences Research Center, University of Hawaii, 1993 East–West Road, Honolulu, HI 96822, United States
- John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, United States
- Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, United States
Kathleen K. Ogata
- John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, United States
- University of Hawaii Kapi’olani Community College, Honolulu, HI 96816, United States
Frederick P. Bellinger
- John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, United States
Thomas Zeyda
- John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, United States

Received 10 November 2008; received in revised form 8 December 2008; accepted 9 December 2008. published online 19 December 2008.

Abstract

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.

Abbreviation: AHP, afterhyperpolarization

Keywords: Afterhyperpolarization, Beta cell, Insulin secretion, SK potassium channel, Heteromeric channel, Diabetic