Single channel characterization of the mitochondrial ryanodine receptor in heart mitoplasts

Shin Young Ryu, Gisela Beutner, Kathleen W. Kinnally, Robert T. Dirksen, Shey Shing Sheu

Research output: Contribution to journalArticlepeer-review

Abstract

Heart mitochondria utilize multiple Ca2+ transport mechanisms. Among them, the mitochondrial ryanodine receptor provides a fast Ca2+ uptake pathway across the inner membrane to control "excitation and metabolism coupling." In the present study, we identified a novel ryanodine-sensitive channel in the native inner membrane of heart mitochondria and characterized its pharmacological and biophysical properties by directly patch clamping mitoplasts. Four distinct channel conductances of ∼100, ∼225, ∼700, and ∼1,000 picosiemens (pS) in symmetrical 150 mM CsCl were observed. The 225 pS cation-selective channel exhibited multiple subconductance states and was blocked by high concentrations of ryanodine and ruthenium red, known inhibitors of ryanodine receptors. Ryanodine exhibited a concentration-dependent modulation of this channel, with low concentrations stabilizing a subconductance state and high concentrations abolishing activity. The 100, 700, and 1,000 pS conductances exhibited different channel characteristics and were not inhibited by ryanodine. Taken together, these findings identified a novel 225 pS channel as the native mitochondrial ryanodine receptor channel activity in heart mitoplasts with biophysical and pharmacological properties that distinguish it from previously identified mitochondrial ion channels.

Original languageEnglish (US)
Pages (from-to)21324-21329
Number of pages6
JournalJournal of Biological Chemistry
Volume286
Issue number24
DOIs
StatePublished - Jun 17 2011

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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