THE METABOTROPIC GLUTAMATE RECEPTORS OF THE VESTIBULAR ORGANS

This research sought to test the presence and function of metabotropic excitatory amino acid receptors (mGluR) in the frog semicircular cana l (SCC). The mGluR agonist +/- 1-aminocyclopentane-trans-1,3-dicarbsxy late (ACPD) produced an increase in afferent firing rates of the ampul lar nerve of the intact posterior canal. This increase was not due to a stimulation of cholinergic efferent terminals or the acetylcholine ( ACh) receptor, since atropine, in concentrations which blocked the res ponse to exogenous acetylcholine, did not affect the response to ACPD. Likewise, ACPD effects were not due to stimulation of postsynaptic NM DA receptors, since the NMDA antagonist D(-)-2-amino-5-phosphonopentan oate (AP-5) did not affect the response to ACPD, reinforcing the repor ted selectivity of ACPD for mGluRs. When the SCC was superfused with a rtificial perilymph known to inhibit hair cell transmitter release (i. e. low Ca-high Mg), ACPD failed to increase afferent firing. This sugg ests that the receptor activated by ACPD is located on the hair cell. Pharmacological evidence suggested that the mGluRs involved in afferen t facilitation belong to Group I (i.e. subtypes 1 and 5). In fact, the Group III agonist AP-4 had no effect, and the ACPD facilitatory effec t was blocked by the Group I mGluR antagonists (S)-4-carboxyphenylglyc ine (CPG) and (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA). Addition al pharmacological evidence supported the presence of Group I mGluRs. Interestingly, the mGluR antagonists, AIDA and 4CPG, by themselves did not affect the resting firing rates of ampullar afferents, This may s uggest that the mGluRs are not involved in resting activity but perhap s only in evoked activity (as suggested in Guth ct al. (1991) Hear. Re s. 56, 69-78). In addition, the mRNA for the mGluR(1) has been detecte d in hair cells of both SCC, utricle, and saccule. In summary, the evi dence points to an lnGluR localized to the hair cell (i.e. an autorece ptor) which may be activated to produce a positive feedback augmentati on of evoked but not resting transmitter release and thus affect affer ent activity. (C) 1998 Elsevier Science B.V. All rights reserved.