Possible role of mitochondria in posttetanic potentiation of GABAergic synaptic transmission in rat neocortical cell cultures.
It has been previously demonstrated that mitochondria are of crucial importance for posttetanic potentiation (PTP) at neuromuscular junction. The aim of our study was to examine whether this may also be the case at a central synapse. To address this question, we studied possible mitochondrial involvement in PTP of GABAergic synaptic transmission in rat neocortical cultures, a preparation in which PTP has not been previously documented. Synaptic responses were evoked by local extracellular stimulation. Whole-cell patch-clamp technique was employed to record inhibitory postsynaptic currents (IPSCs) from postsynaptic neurons. Tetanic stimulation (30 Hz, 4 s) of the presynaptic neuron evoked an increase of IPSC amplitude, lasting for about 1 min. PTP was accompanied by a decrease of coefficient of variation of the IPSC and a decrease of paired-pulse (IPSC(2)/IPSC(1)) ratio, indicating involvement of presynaptic mechanism(s) in PTP. Possible role of mitochondria in PTP was addressed using drugs affecting Ca(2+) uptake and subsequent Ca(2+) efflux: carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and tetraphenylphosphonium ions (TPP(+)). It was found that both CCCP (1-2 microM) and TPP(+) (10 microM) either substantially decreased or eliminated PTP. These results further confirm presynaptic origin of PTP in neocortical neurons and suggest an important role of mitochondrial Ca(2+) turnover in this form of synaptic plasticity at the central synapse.
Storozhuk
Maksim V
MV
A.A. Bogomoletz Institute of Physiology, Kiev, Ukraine. maksim@biph.kiev.ua
Ivanova
Svetlana Y
SY
Balaban
Pavel M
PM
Kostyuk
Platon G
PG
D000818:Animals; D000831:Animals, Newborn; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D008928:Mitochondria / Q000502:physiology*; D019579:Neocortex / Q000166:cytology*; D009433:Neural Inhibition / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000502:physiology / Q000528:radiation effects; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D013997:Time Factors; D014475:Uncoupling Agents / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D014475:Uncoupling Agents; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D005680:gamma-Aminobutyric Acid