Exogenously applied KYNA suppressed spontaneous glutamatergic
activity in the hippocampal samples obtained from patients with MTLE-HS
To investigate the role of exogenously applied KYNA on glutamatergic
neurotransmission, the tissue slices of the above-mentioned groups were
perfused with 10 µM KYNA for 30
mins. The frequency and amplitude were significantly reduced after 30
mins perfusion of KYNA in comparison to those of basal values in both
groups (Table 1). The cumulative distribution of inter-event intervals
displaced toward longer interval and that of peak amplitudes displaced
towards shorter amplitude (Figure 5b, c and e, f). However, Rise time
and τd was not affected (Table 1). The magnitude of
percentage reduction of the frequency was significantly enhanced in the
hippocampal samples in comparison to the non-seizure controls (16.34±
0.92% in non-seizure control vs 30.72 ± 1.87% in MTLE-HS; Figure 5g).
At low micro molecular concentration, KYNA predominantly exerts
inhibition through NMDA receptors; but in the present scenario,
inhibitory action of KYNA was significantly enhanced in case of MTLE-HS
which may be due to upregulation of NMDA receptors. Now, to investigate
the contribution of inhibitory action of KYNA mediated through the NMDA
receptors, the slices were perfused with 50µM APV alone for 10 mins
which blocked only NMDA receptors. APV suppressed the frequency by 42.83
± 2.26% in the non-seizure controls and 58.17 ± 2.06% in the MTLE-HS
group respectively (Figure 5h and i) with a significant difference
between the two groups suggesting the role of enhanced tonic NMDA
receptor activity in altered synaptic transmission in the hippocampal
samples of the MTLE-HS patients. For KYNA, the magnitude of reduction of
the frequency was significantly reduced than that of APV (Figure 5j),
suggesting that although its primary target are NMDA receptors, but it
also has some target sites which are different from it.