Burst kinetics of co-expressed Kir6.2/SUR1 clones: Comparison of recombinant with native ATP-sensitive K+ channel behavior

A. E. Alekseev, M. E. Kennedy, B. Navarro, A. Terzic

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Co-expression of clones encoding Kir6.2, a K+ inward rectifier, and SUR1, a sulfonylurea receptor, reconstitutes elementary features of ATP-sensitive K+ (K(ATP)) channels. However, the precise kinetic properties of Kir6.2/SUR1 clones remain unknown. Herein, intraburst kinetics of Kir6.2/SUR1 channel activity, heterologously co-expressed in COS cells, displayed mean closed times from 0.7 ± 0.1 to 0.4 ± 0.03 msec, and from 0.4 ± 0.1 to 2.0 ± 0.2 msec, and mean open times from 1.9 ± 0.4 to 4.5 ± 0.8 msec, and from 12.1 ± 2.4 to 5.0 ± 0.2 msec between -100 and -20 mV, and +20 to +80 mV, respectively. Burst duration for Kir6.2/SUR1 activity was 17.9 ± 1.8 msec with 5.6 ± 1.5 closings per burst. Burst kinetics of the Kir6.2/SUR1 activity could be fitted by a four-state kinetic model defining transitions between one open and three closed states with forward and backward rate constants of 1905 ± 77 and 322 ± 27 sec-1 for intraburst, 61.8 ± 6.6 and 23.9 ± 5.8 sec-1 for interburst, 12.4 ± 6.0 and 13.6 ± 2.9 sec-1 for intercluster events, respectively. Intraburst kinetic properties of Kir6.2/SUR1 clones were essentially indistinguishable from pancreatic or cardiac K(ATP) channel phenotypes, indicating that intraburst kinetics per se were insufficient to classify recombinant Kir6.2/SUR1 amongst native K(ATP) channels. Yet, burst kinetic behavior of Kir6.2/SUR1 although similar to pancreatic, was different from that of cardiac K(ATP) channels. Thus, expression of Kir6.2/SUR1 proteins away from the pancreatic microenvironment, confers the burst kinetic identity of pancreatic, but not cardiac K(ATP) channels. This study reports the kinetic properties of Kir6.2/SUR1 clones which could serve in the further characterization of novel K(ATP) channel clones.

Original languageEnglish (US)
Pages (from-to)161-168
Number of pages8
JournalJournal of Membrane Biology
Volume159
Issue number2
DOIs
StatePublished - Oct 14 1997

Keywords

  • ABC binding cassette
  • Cardiac
  • Inward rectifier K channel
  • K(ATP) channels
  • Kinetic model
  • Pancreas

ASJC Scopus subject areas

  • Biophysics
  • Physiology
  • Cell Biology

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