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Isoflurane Increases Mitochondrial Free Ca 2+ by Attenuating the Na + /Ca 2+ Exchanger Activity
Author(s) -
Agarwal Bhawana,
Camara Amadou K.S.,
Stowe David F.,
Bosnjak Zeljko J.,
Beard Daniel A.,
Dash Ranjan K.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.888.4
Subject(s) - isoflurane , chemistry , mitochondrion , anesthetic , biophysics , oxygen , redox , depolarization , biochemistry , anesthesia , inorganic chemistry , biology , medicine , organic chemistry
Volatile anesthetics protect against cardiac ischemia/perfusion (IR) injury. Excess mitochondrial free Ca 2+ ([Ca 2+ ] m ) is a major cause of mitochondria ‐mediated IR injury. To better understand mechanisms of anesthetic ‐mediated protection of mitochondrial function, we monitored time courses of NADH redox state, respiration, ΔΨ m , and matrix Ca 2+ uptake/efflux kinetics during anesthetic exposure. Isolated mitochondria from rat hearts were energized with 10 mM Na + ‐or K + ‐pyruvate+malate, or with Na + ‐succinate followed by isoflurane (0.5 to 2 mM), CaCl 2 (≈ 200 nM free Ca 2+ ), and ADP (250 μM). Our data showed that isoflurane: (a) increased [Ca 2+ ] m despite ΔΨ m depolarization, while decreasing Na + ‐dependent Ca 2+ efflux (NCE), (b) decreased state 3 NADH oxidation and increased state 3 duration with Na + ‐pyruvate/malate, but c) caused no change in state 3 NADH oxidation but reduced state 3 duration with Na + ‐succinate. These data indicate that isoflurane (1) increases [Ca 2+ ] m by attenuating activity of NCE and, (2) decreases the rate of ADP phosphorylation while reducing the duration of state 3 respiration by attenuating complex I activity. Isoflurane's effects on inhibiting NCE and complex I together may act as the protective mechanism against IR injury at the mitochondrial level.