Pathway-specific variants of AMPA receptors and their contribution to neuronal signaling.

Neurons of the nucleus magnocellularis (nMAG) of the chick express AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate) receptors displaying unusually rapid kinetics of desensitization (Raman and Trussell, 1992a). To investigate whether fast AMPA receptors are present in other auditory neurons, we compared the properties of AMPA receptors in auditory as well as nonauditory cells. These included neurons of nMAG, the nucleus angularis, the nucleus laminaris, the cochlear ganglion, the Purkinje cell layer of the cerebellum, the ventral horn of the spinal cord, and the brainstem nucleus of the glossopharyngeal nerve (ncIX). Rapid application of glutamate to voltage-clamped outside-out membrane patches indicated that AMPA receptors in the four types of auditory cells had significantly faster kinetics of desensitization than did the three types of nonauditory neurons. Channel kinetics in auditory (nMAG) and nonauditory (ncIX) cells were also compared by means of spectral analysis and the time course of current deactivation upon removal of glutamate. Both techniques revealed a burst duration for nMAG channels of 400-500 musec at room temperature, two to three times shorter than for ncIX cells. Single channels in nMAG had a burst duration of 550 musec and an open time of approximately 150 musec. Miniature excitatory postsynaptic currents of brainstem auditory neurons in slices were also brief, with decay constants of 150-250 musec at 29-32 degrees C. We demonstrated that the fast kinetics of this AMPA receptor are physiologically important, since cyclothiazide, which reduces desensitization and prolongs synaptic currents, doubled the relative refractory period of orthodromic spikes in nMAG cells in brain slices. We conclude that auditory brainstem neurons express a specialized subtype of AMPA receptors. This "fast" AMPA receptor may be useful in transmitting signals necessary for sound localization.