Please use this identifier to cite or link to this item:
|Title:||Presynaptic mitochondrial calcium sequestration influences transmission at mammalian central synapses|
Forsythe, Ian D.
|Publisher:||Society for Neuroscience|
|Citation:||Journal of Neuroscience, 2002, 22 (14), pp.5840-5847|
|Abstract:||Beyond their role in generating ATP, mitochondria have a high capacity to sequester calcium. The interdependence of these functions and limited access to presynaptic compartments makes it difficult to assess the role of sequestration in synaptic transmission. We addressed this important question using the calyx of Held as a model glutamatergic synapse by combining patch-clamp with a novel mitochondrial imaging method. Presynaptic calcium current, mitochondrial calcium concentration ([Ca2+]mito, measured using rhod-2 or rhod-FF), cytoplasmic calcium concentration ([Ca2+]cyto, measured using fura-FF), and the postsynaptic current were monitored during synaptic transmission. Presynaptic [Ca2+]cytorose to 8.5 ± 1.1 μM and decayed rapidly with a time constant of 45 ± 3 msec; presynaptic [Ca2+]mito also rose rapidly to >5 μM but decayed slowly with a half-time of 1.5 ± 0.4 sec. Mitochondrial depolarization with rotenone and carbonyl cyanidep-trifluoromethoxyphenylhydrazone abolished mitochondrial calcium rises and slowed the removal of [Ca2+]cyto by 239 ± 22%. Using simultaneous presynaptic and postsynaptic patch clamp, combined with presynaptic mitochondrial and cytoplasmic imaging, we investigated the influence of mitochondrial calcium sequestration on transmitter release. Depletion of ATP to maintain mitochondrial membrane potential was blocked with oligomycin, and ATP was provided in the patch pipette. Mitochondrial depolarization raised [Ca2+]cyto and reduced transmitter release after short EPSC trains (100 msec, 200 Hz); this effect was reversed by raising mobile calcium buffering with EGTA. Our results suggest a new role for presynaptic mitochondria in maintaining transmission by accelerating recovery from synaptic depression after periods of moderate activity. Without detectable thapsigargin-sensitive presynaptic calcium stores, we conclude that mitochondria are the major organelle regulating presynaptic calcium at central glutamatergic terminals.|
|Rights:||Creative Commons Attribution License|
|Appears in Collections:||Published Articles, MRC Toxicology Unit|
Files in This Item:
|5840.full.pdf||Publisher version||298.19 kB||Adobe PDF||View/Open|
Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.