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Modulatory effects of endogenous nitric oxide on the bioenergetics of BK Ca channels in guinea pig isolated cardiac mitochondria
Author(s) -
Ver Matthew R,
Camara Amadou KS,
Aldakkak Mohammed,
Heinen Andre,
Stowe David F
Publication year - 2006
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.20.5.a893-c
Subject(s) - mitochondrion , chemistry , nitric oxide , respiration , bioenergetics , cytochrome c oxidase , biophysics , oxidase test , nitric oxide synthase , membrane potential , biochemistry , enzyme , biology , anatomy , organic chemistry
Plasmalemmal studies have shown that exogenous nitric oxide (NO) promotes big‐conductance Ca 2+ ‐sensitive K + (BK Ca ) channel opening, but it is unknown if NO interacts with putative BK Ca channels in the mitochondrial inner membrane. The presence of a mitochondrial NO synthase (NOS) is established, and studies support involvement of NO in regulating respiration by competing with the O 2 binding site on cytochrome oxidase. We examined the effects of 500 μM L‐NIO, a NOS inhibitor, and 5 μM paxilline (PAX), a BK Ca channel inhibitor, in mitochondria respiring on succinate at 37°C. Mitochondria respired in state II until O 2 fell from about 222 to 67 μM before addition of 10 μM NS1619, a BK Ca channel opener, and then 500 μM ADP (onset of state III). L‐NIO and NS1619 independently increased state III respiration rate by 8.0±1.0% and 8.4±1.8%, respectively, and together by 16.1±1.5%. State II respiration was also increased by 5.2±1.1% with NS1619, but was unaffected by L‐NIO. PAX abolished the effects of NS1619 on respiration, but did not change the effect of L‐NIO. Our study indicates that L‐NIO and NS1619 enhance respiration by independent mechanisms, i.e., removal of the inhibitory effect of NO on cytochrome oxidase, and K + /H + exchange with matrix K + influx. It remains unclear from these results alone if interaction of NO occurs at the level of the mitochondrial BK Ca channel as suggested at the plasmalemmal level. (NIH, AHA)