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FH Andrade; Rat Extraocular Muscles Use Mitochondria as Fast Calcium Sinks . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1911.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Recent studies suggest that mitochondria can function as effective cellular calcium sinks in a variety of systems that demand extremely fast calcium transients. The fast and shallow twitches and rightward shift in the force-stimulation frequency relationship typically seen in whole rat extraocular muscles (EOMs) may be explained in part by faster calcium kinetics during contractile events. Therefore, the working hypothesis was that mitochondria constitute a separate calcium-sequestering compartment that regulates force production in rat EOMs during submaximal contractions. Methods: Superior rectus (the index EOM) and lateral omohyoid (LO, relatively mitochondria-poor) muscles were dissected from 45-day old male Sprague-Dawley rats, and placed in a small perfusion chamber between a force transducer and a micropositioner. The chamber was then mounted on the stage of a microscope equipped for calcium-specific spectrophotometry using indo-1. Force and cytosolic calcium concentration ([Ca2+]i) transients during isometric contractions, and their response to specific pharmacological interventions were measured. Results: The ionophore calcimycin (1 µM) and caffeine (5 mM) significantly increased resting [Ca2+]i in LO (22356 and 15415% over control, respectively, P<0.001), but not in EOMs (167 and 142% over control, P≷0.05). Carbonyl cyanide m-chlorophenyl hydrazone (CCCP, 10 µM, inhibits calcium influx to mitochondria) induced marked increases in maximal tetanic [Ca2+]i (738% over control, P<0.001) in EOMs, with a much smaller effect in the LO (143% over control, P<0.05). CCCP also increased [Ca2+]i and force during submaximal contractions (∼50% of maximal force) to a greater extent in EOMs (≷25%) compared to LO (<10%). Conclusions: These data support the initial hypothesis and indicate that mitochondria are physiological regulators of the calcium transients during rat EOM contractions. Apparently, the rapid movement of calcium in and out of the mitochondria is enough to influence the extremely fast contractile events typical of EOMs. This may be an important factor in determining the wide frequency-response range, and fast relaxation rate of rat EOMs.
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