Nanomolar free calcium enhances oxidative phosphorylation. However, the effects over a broad concentration range, at different respiratory states, or on specific energy substrates are less clear. We examined the action of varying [Ca(2+)] over respiratory states ranging 4 to 3 on skeletal muscle mitochondrial respiration, potential, ATP production, and H2O2 production using ADP recycling to clamp external [ADP]. 450 nM calcium enhanced respiration in mitochondria energized by the complex I substrates, glutamate/malate (but not succinate) at [ADP] of 4-256 µM, but more substantially at intermediate respiratory states and not all at state 4. Using varied [Ca(2+)], we found that the stimulatory effects on respiration and ATP production were most prominent at nanomolar concentrations, but inhibitory at 10 µM or higher. ATP production decreased more than respiration at 10 µM calcium. However, potential continued to increase up to 10 µM; suggesting a calcium-induced inability to utilize potential for phosphorylation independent of opening of the mitochondrial permeability transition pore (MTP). This effect of 10 µM calcium was confirmed by direct determination of ATP production over a range of potential created by differing substrate concentrations. Consistent with past reports, nanomolar [Ca(2+)] had a stimulatory effect on utilization of potential for phosphorylation. Increasing [Ca(2+)] was positively and continuously associated with H2O2 production. In summary, the stimulatory effect of calcium on mitochondrial function is substrate dependent and most prominent over intermediate respiratory states. Calcium stimulates or inhibits utilization of potential for phosphorylation dependent on concentration with inhibition at higher concentration independent of MTP opening.
Pharmacology, Toxicology and Pharmaceutical Science
3
4%
Other
8
10%
Unknown
24
31%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 February 2025.
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#23,088,418
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Outputs from American Journal of Physiology: Cell Physiology
#3,516
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Outputs of similar age
#224,532
of 361,550 outputs
Outputs of similar age from American Journal of Physiology: Cell Physiology
#23
of 31 outputs
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