Diabetes mellitus reduces the function and expression of ATP-dependent K+ channels in cardiac mitochondria

Ibra S. Fancher, Gregory M. Dick, John M. Hollander

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Aim Our goal was to determine the effects of type I diabetes mellitus on the function and expression of ATP-dependent K+ channels in cardiac mitochondria (mitoKATP), composed of a pore-forming subunit (Kir6.1) and a diazoxide-sensitive sulphonylurea receptor (SUR1). We tested the hypothesis that diabetes reduces Kir6.1 and SUR1 expression as well as diazoxide-induced depolarization of mitochondrial membrane potential (ΔΨm). Main methods Male FVB mice were made diabetic for 5 weeks with multiple low dose injections of streptozotocin. Cardiac mitochondria were separated into two populations: subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM). mitoKATP expression was determined via Western blot analysis of Kir6.1 and SUR1 proteins. mitoKATP function was determined by measuring ΔΨm with the potentiometric dye rhodamine 123. Key findings Diabetes reduced Kir6.1 and SUR1 expression in IFM by over 40% (p < 0.05 for both). Similarly, diabetes reduced Kir6.1 expression in SSM by approximately 40% (p < 0.05); however, SUR1 expression was unaffected. Opening mitoKATP with diazoxide (100 μM) depolarized control IFM ΔΨm by 80% of the valinomycin maximum; diabetic IFM depolarized only 30% (p < 0.05). Diazoxide-induced depolarization was much less in SSM (20-30%) and unaffected by diabetes. Significance Our data indicate that diabetes reduces mitoKATP expression and function in IFM. These changes in mitoKATP may provide an opportunity to understand mechanisms leading to diabetic cardiomyopathy and loss of cardioprotective mechanisms in the diabetic heart.

Original languageEnglish
Pages (from-to)664-668
Number of pages5
JournalLife Sciences
Volume92
Issue number11
DOIs
StatePublished - 2013

Keywords

  • Diazoxide interfibrillar
  • Kir6.1
  • Membrane potential
  • SUR1
  • Subsarcolemmal
  • mitoK

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