Epileptogenesis up-regulates metabotropic glutamate receptor activation of sodium-calcium exchange current in the amygdala.

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Abstract
Postsynaptic metabotropic glutamate (mGlu) receptor-activated inward current mediated by Na+-Ca2+ exchange was compared in basolateral amygdala (BLA) neurons from brain slices of control (naı̈ve and sham-operated) and amygdala-kindled rats. In control neurons, the mGlu agonist, quisqualate (QUIS; 1–100 μM), evoked an inward current not associated with a significant change in membrane slope conductance, measured from current-voltage relationships between −110 and −60 mV, consistent with activation of the Na+-Ca2+ exchanger. Application of the group I selective mGlu receptor agonist ( S)-3,5-dihydroxyphenylglycine [( S)-DHPG; 10–1000 μM] or the endogenous agonist, glutamate (10–1000 μM), elicited the exchange current. QUIS was more potent than either ( S)-DHPG or glutamate (apparent EC50 = 19 μM, 57 μM, and 0.6 mM, respectively) in activating the Na+-Ca2+ exchange current. The selective mGlu5 agonist, ( R,S)-2-chloro-5-hydroxyphenylglycine [( R,S)-CHPG; apparent EC50 = 2.6 mM] also induced the exchange current. The maximum response to ( R,S) -DHPG was about half of that of the other agonists suggesting partial agonist action. Concentration-response relationships of agonist-evoked inward currents were compared in control neurons and in neurons from kindled animals. The maximum value for the concentration-response relationship of the partial agonist ( S)-DHPG- (but not the full agonist- [QUIS or ( R, S)-CHPG]) induced inward current was shifted upward suggesting enhanced efficacy of this agonist in kindled neurons. Altogether, these data are consistent with a kindling-induced up-regulation of a group I mGlu-, possibly mGlu5-, mediated responses coupled to Na+-Ca2+ exchange in BLA neurons.