The Journal of Neurophysiology Vol. 83 No. 4 April 2000, pp. 2458-2462
Copyright ©2000 by the American Physiological Society

RAPID COMMUNICATION

Epileptogenesis Up-Regulates Metabotropic Glutamate Receptor Activation of Sodium-Calcium Exchange Current in the Amygdala

Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, Texas 77555-1031

Keele, N. Bradley, Fatiha Zinebi, Volker Neugebauer, and P. Shinnick-Gallagher. Epileptogenesis Up-Regulates Metabotropic Glutamate Receptor Activation of Sodium-Calcium Exchange Current in the Amygdala. J. Neurophysiol. 83: 2458-2462, 2000. 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 (naïve 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.