Third Place—Resident Basic Science Award 1997: Inhibition of Nitric Oxide Synthase Causes Elevation of Hearing Thresholds

Abstract

OBJECTIVE: Nitric oxide mediates the effects of excitatory amino acids in the central nervous system. The excitatory amino acids are thought to be the neurotransmitters at the cochlear hair cell-afferent nerve synapse. Nitric oxide synthase is present in spiral ganglion cells. This study investigated the role of nitric oxide in cochlear neurotransmission.

METHODS: In gerbils, cochlear compound action potential thresholds were recorded before and after cochlear perfusions with control solutions of artificial perilymph solution and test solutions of S-methyl-L-thiocitrulline (MTC), a competitive inhibitor of nitric oxide synthase. Cochleas were also pre-perfused with L-arginine before perfusion with a mixture of MTC/L-arginine (to overcome competitive inhibition by MTC with L-arginine, the natural substrate of nitric oxide synthase).

RESULTS: Cochlear perfusion with MTC caused significant elevations of compound action potential threshold of 51 dB as opposed to insignificant elevations of only 10 dB in control animals. An insignificant threshold shift of 9 dB was observed when L-arginine was coperfused with MTC.

CONCLUSIONS: Nitric oxide is involved in neurotransmission/neuromodulation in the cochlea. Because nitric oxide is both a mediator of neurotoxicity and an initiator of apoptosis in the central nervous system, nitric oxide may play a role in these processes in the cochlea.

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