Lactic acid modulates excitatory synaptic transmission at the calyx of Held

GONZÁLEZ INCHAUSPE C; DI GUILMI, MN; UCHITEL, OD.

San Diego

Congreso; 43th Annual Meeting of Society for Neuroscience; 2013

Society for Neuroscience

Lactic acid is produced by anaerobic metabolism during physiological and pathological conditions in different sites: from muscle to brain. As a consequence, the pH in-vivo can fall as low as 6.5. The mechanism of action is still unclear but it was proposed an indirect role that would increase the activity of an acid-sensing ion channels (ASICs) and a direct role as a chelator of extracellular divalent ions (Immke and McCleskey, 2001). In this work we studied the effect of lactic acid on synaptic transmission using the calyx of Held-MNTB giant excitatory glutamatergic synapse in the mammalian central nervous system. Lactic acid (15 mM) enhanced ASIC currents evoked in postsynaptic MNTB neuron by a rapid drop in extracellular pH (reversible after washout). In addition, lactic acid decreased EPSC amplitudes as well the depression rate during high frequency trains at 100 and 300 Hz. The addition of extra calcium and magnesium to aCSF, reaching values of 2.35 Ca2+/1.12 Mg+ (Immke and McCleskey, 2001), partially restored the original short term depression feature. These data suggest a direct role of lactic acid on synaptic transmission in addition to its role as a chelator of divalent ions and as modulator of postsynaptic ASIC channels.