Research ArticleCalcium signaling

L-type Ca2+ channel–mediated Ca2+ influx adjusts neuronal mitochondrial function to physiological and pathophysiological conditions

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Science Signaling  11 Feb 2020:
Vol. 13, Issue 618, eaaw6923
DOI: 10.1126/scisignal.aaw6923

A reversal to limit neuronal death

Ca2+ ions are an important second messenger, but excessive Ca2+ mitochondrial influx from the cytoplasm can trigger cell death. In response to depolarizing stimuli, L-type Ca2+ channels mediate Ca2+ entry into neurons. Hotka et al. found that the effect of L-type Ca2+ channel activity on mitochondrial Ca2+ concentrations depended on the strength of the depolarizing stimulus applied to neurons. Stimuli of moderate strength enhanced the production of ATP by ATP synthase. In contrast, stronger depolarizing stimuli caused the ATP synthase to operate in reverse mode and consume ATP, which helped to limit increases in mitochondrial Ca2+. These results may explain why neuroprotection is seen not only with blockers of L-type Ca2+ channel activity but also with compounds that stimulate channel activity.

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