PT  - JOURNAL ARTICLE
AU  - Ruusuvuori, Eva
AU  - Kirilkin, Ilya
AU  - Pandya, Nikhil
AU  - Kaila, Kai
TI  - Spontaneous Network Events Driven by Depolarizing GABA Action in Neonatal Hippocampal Slices are Not Attributable to Deficient Mitochondrial Energy Metabolism
AID  - 10.1523/JNEUROSCI.3355-10.2010
DP  - 2010 Nov 17
TA  - The Journal of Neuroscience
PG  - 15638--15642
VI  - 30
IP  - 46
4099  - http://www.jneurosci.org/content/30/46/15638.short
4100  - http://www.jneurosci.org/content/30/46/15638.full
SO  - J. Neurosci.2010 Nov 17; 30
AB  - In two recent papers (Rheims et al., 2009; Holmgren et al., 2010), Zilberter and coworkers argue that the well known depolarizing GABA actions that take place at the cellular and network level in the neonatal hippocampus and neocortex in vitro are pathophysiological phenomena, attributable to deficient mitochondrial energy metabolism. In their experiments, supplementing the glucose-containing solution with weak-acid substrates of mitochondrial energy metabolism (such as β-hydroxy-butyrate, lactate, or pyruvate) abolished the spontaneous network events (giant depolarizing potentials; GDPs) and the underlying depolarizing actions of GABA. In this study, we made electrophysiological recordings of GDPs and monitored the mitochondrial membrane potential (Ψm) and intracellular pH (pHi) in CA3 neurons in neonatal rat hippocampal slices. Supplementing the standard physiological solution with l-lactate did not produce a change in Ψm, whereas withdrawal of glucose, in the presence or absence of l-lactate, was followed by a pronounced depolarization of Ψm. Furthermore, d-lactate (a poor substrate of mitochondrial metabolism) caused a prompt inhibition in GDP frequency which was similar to the effect of l-lactate. The suppression of GDPs was strictly proportional to the fall in pHi caused by weak carboxylic acids (l-lactate, d-lactate, or propionate) or by an elevated CO2. The main conclusions of our work are that the inhibitory effect of l-lactate on GDPs is not mediated by mitochondrial energy metabolism, and that glucose at its standard 10 mm concentration is an adequate energy substrate for neonatal neurons in vitro. Notably, changes in pHi appear to have a very powerful modulatory effect on GDPs.