Inhibition of mitochondrial Ca2+ uptake affects phasic release from motor terminals differently depending on external [Ca2+ |
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Authors: | Talbot Janet D David Gavriel Barrett Ellen F |
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Institution: | Department of Physiology and Biophysics, University of Miami School of Medicine, Miami, Florida 33136, USA. |
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Abstract: | We investigated how inhibition of mitochondrial Ca2+ uptake affects stimulation-induced increases in cytosolic Ca2+] and phasic and asynchronous transmitter release in lizard motor terminals in 2 and 0.5 mM bath Ca2+]. Lowering bath Ca2+] reduced the rate of rise, but not the final amplitude, of the increase in mitochondrial Ca2+] during 50-Hz stimulation. The amplitude of the stimulation-induced increase in cytosolic Ca2+] was reduced in low-bath Ca2+] and increased when mitochondrial Ca2+ uptake was inhibited by depolarizing mitochondria. In 2 mM Ca2+, end-plate potentials (epps) depressed by 53% after 10 s of 50-Hz stimulation, and this depression increased to 80% after mitochondrial depolarization. In contrast, in 0.5 mM Ca2+ the same stimulation pattern increased epps by approximately 3.4-fold, and this increase was even greater (transiently) after mitochondrial depolarization. In both 2 and 0.5 mM Ca2+], mitochondrial depolarization increased asynchronous release during the 50-Hz train and increased the total vesicular release (phasic and asynchronous) measured by destaining of the styryl dye FM2-10. These results suggest that by limiting the stimulation-induced increase in cytosolic Ca2+], mitochondrial Ca2+ uptake maintains a high ratio of phasic to asynchronous release, thus helping to sustain neuromuscular transmission during repetitive stimulation. Interestingly, the quantal content of the epp reached during 50-Hz stimulation stabilized at a similar level ( approximately 20 quanta) in both 2 and 0.5 mM Ca2+. A similar convergence was measured in oligomycin, which inhibits mitochondrial ATP synthesis without depolarizing mitochondria, but quantal contents fell to <20 when mitochondria were depolarized in 2 mM Ca2+. |
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