Hybrid assemblies of ATP-sensitive K+ channels determine their muscle-type-dependent biophysical and pharmacological properties

Domenico Tricarico, Antonietta Mele, Andrew L. Lundquist, Reshma R. Desai, Alfred L. George, Diana Conte Camerino*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

ATP-sensitive K+ channels (KATP) are an octameric complex of inwardly rectifying K+ channels (Kir6.1 and Kir6.2) and sulfonylurea receptors (SUR1 and SUR2A/B), which are involved in several diseases. The tissue-selective expression of the subunits leads to different channels; however, the composition and role of the functional channel in native muscle fibers is not known. In this article, the properties of KATP channels of fast-twitch and slow-twitch muscles were compared by combining patch-clamp experiments with measurements of gene expression. We found that the density of KATP currents/area was muscle-type specific, being higher in fast-twitch muscles compared with the slow-twitch muscle. The density of KATP currents/area was correlated with the level of Kir6.2 expression. SUR2A was the most abundant subunit expressed in all muscles, whereas the vascular SUR2B subunit was expressed but at lower levels. A significant expression of the pancreatic SUR1 was also found in fast-twitch muscles. Pharmacological experiments showed that the channel response to the SUR1 agonist diazoxide, SUR2A/B agonist cromakalim, SUR1 antagonist tolbuiamide, and the SUR1/SUR2A/B-antagonist glibenclamide matched the SURs expression pattern. Muscle-specific KATP subunit compositions contribute to the physiological performance of different muscle fiber types and determine the pharmacological actions of drugs modulating KATP activity in muscle diseases.

Original languageEnglish (US)
Pages (from-to)1118-1123
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number4
DOIs
StatePublished - Jan 24 2006

Keywords

  • Pharmacology
  • Physiology
  • Skeletal muscle

ASJC Scopus subject areas

  • General

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