Comparison of Glutamate Turnover in Nerve Terminal

Authors: Anant B Patel James C K Lai Golam I M Chowdhury Douglas L Rothman Kevin L Behar

Publish Date: 2016/12/26

Volume: 42, Issue: 1, Pages: 173-190

PDF Link

Abstract

The 13C turnover of neurotransmitter amino acids glutamate GABA and aspartate were determined from extracts of forebrain nerve terminals and brain homogenate and frontoparietal cortex from anesthetized rats undergoing timed infusions of 1613C2glucose or 213Cacetate Nerve terminal 13C fractional labeling of glutamate and aspartate was lower than those in whole cortical tissue at all times measured up to 120 min suggesting either the presence of a constant dilution flux from an unlabeled substrate or an unlabeled effectively noncommunicating on the measurement timescale glutamate pool in the nerve terminals Half times of 13C labeling from 1613C2glucose as estimated by least squares exponential fitting to the time course data were longer for nerve terminals GluC4 218 min GABAC2 210 min compared to cortical tissue GluC4 124 min GABAC2 145 min except for AspC3 which was similar 265 vs 270 min The slower turnover of glutamate in the nerve terminals but not GABA compared to the cortex may reflect selective effects of anesthesia on activitydependent glucose use which might be more pronounced in the terminals The 13C labeling ratio for glutamateC4 from 213Cacetate over that of 13Cglucose was twice as large in nerve terminals compared to cortex suggesting that astroglial glutamine under the 13C glucose infusion was the likely source of much of the nerve terminal dilution The net replenishment of most of the nerve terminal amino acid pools occurs directly via trafficking of astroglial glutamineWe thank Bei Wang for assistance with animal preparation and Terry Nixon Peter Brown and Scott McIntire for the maintenance of the NMR spectrometer and related equipment in the Yale Magnetic Resonance Research Center The assistance of Dr Graeme Mason in the implementation of the MonteCarlo fitting routines within the CWave software was greatly appreciated

Keywords: