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Isoflurane induces substrate‐dependent early mitochondrial PTP opening (648.13)
Author(s) -
Agarwal Bhawana,
Dash Ranjan,
Bosnjak Zeijko,
Stowe David,
Camara Amadou
Publication year - 2014
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.28.1_supplement.648.13
Subject(s) - mptp , mitochondrial permeability transition pore , mitochondrion , isoflurane , chemistry , ryanodine receptor , biophysics , pharmacology , biochemistry , apoptosis , biology , endocrinology , receptor , programmed cell death , dopamine , organic chemistry , dopaminergic
The volatile anesthetic isoflurane (ISO) may increase permeability of mitochondria to protect against mitochondrial injury. Prolonged opening of the mitochondrial permeability transition pore (mPTP) inevitably causes mitochondrial demise, whereas transient mPTP opening may release accumulated Ca 2+ from the matrix to avoid subsequent irreversible mPTP opening due to Ca 2+ overload. To test if ISO alters mPTP opening, we isolated mitochondria from Wistar rat hearts to assess buffer Ca 2+ uptake by Fura 4F. We found that: (a) ISO (1 mM) induced earlier mPTP opening by increasing Ca 2+ uptake rate with succinate (SUC). (b) ISO did not alter mPTP opening but reduced Ca 2+ uptake with pyruvate/malate. (c) 10 µM ryanodine or 10 nM imperatoxin A with SUC increased Ca 2+ uptake and induced earlier mPTP opening; this suggests that ISO’s effects on mPTP may be due to increased conductance via mitochondrial ryanodine receptors (mRyR). We have patch‐clamped single mRyRs in mitoplasts. Our data infer indirectly that SUC substrate ‐dependent transient mPTP opening may be due to enhanced RyR Ca 2+ uptake. Transient Ca 2+ release could be a mechanism underlying ISO –induced cardiac protection in ischemia‐reperfusion injury. Grant Funding Source : P01‐GM066730, R01‐HL095122, R01‐HL089514