Evidence for a unique long chain Acyl-CoA ester binding site on the ATP- regulated potassium channel in mouse pancreatic beta cells

Robert Bränström, Barbara E. Corkey, Per Olof Berggren, Olof Larsson

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

The mechanism by which long chain acyl-CoA (LC-CoA) esters affect the ATF-regulated potassium channel (K(ATP) channel) was studied in inside-out patches isolated from mouse pancreatic beta cells. Addition of LC-CoA esters dramatically increased K(ATP) channel activity. The stimulatory effect of the esters could be explained by the induction of a prolonged open state of the channel and did not involve alterations in single channel unitary conductance. Under control conditions, absence of adenine nucleotides, the distribution of K(ATP) channel open time could be described by a single exponential, with a time constant of about 25 ms. Exposing the same patch to LC-CoA esters resulted in the appearance of an additional component with a time constant of >150 ms, indicating a conformational change of the channel protein. LC-CoA esters were also able to potently activate channel activity at different ratios of ATP/ADP. Simultaneous additions of MgADP and LC-CoA esters resulted in a supra-additive effect on channel mean open time, characterized by openings of very long duration. Following modification of the K(ATP) channel by a short exposure of the patch to the protease trypsin, the stimulatory effect of ADP on channel activity was lost while activation by LC-CoA esters still persisted. This indicates that LC-CoA esters and MgADP do not bind to the same site. We conclude that LC-CoA esters may play an important role in the physiological regulation of the K(ATP) channel in the pancreatic beta cell by binding to a unique site and thereby inducing repolarization of the beta cell-membrane potential.

Original languageEnglish (US)
Pages (from-to)17390-17394
Number of pages5
JournalJournal of Biological Chemistry
Volume272
Issue number28
DOIs
StatePublished - Aug 5 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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