Calcitonin gene-related peptide suppresses hair cell responses to mechanical stimulation in the Xenopus lateral line organ.

The presence of calcitonin gene-related peptide (CGRP) in the efferent fibers of virtually every hair cell organ studied suggests it may serve some fundamental but heretofore unknown role in control of hair cell function. We examined the effects of CGRP on spontaneous and stimulus-evoked discharge patterns in an in vitro preparation of the lateral line organ of Xenopus laevis. Discharge patterns were determined by sinusoidally displacing the cupula with a glass micropipette driven with a piezoelectric device while recording afferent fiber activity. All afferent fibers had characteristic frequencies of 16-32 Hz. Responses synchronized to cupular displacements as small as 20 nm. CGRP suppressed responses of the lateral line organ to displacement while increasing spontaneous discharge rate. In the presence of CGRP, stimulus-response curves were shifted 10 dB toward higher displacement levels. The suppression of stimulus-evoked responses suggests a function for CGRP as an efferent neurotransmitter that is similar to that of cholinergic efferent transmission in other hair cell organs. The 10 dB shift toward larger displacements makes it comparable in magnitude with the effects of electrical stimulation of efferents in the mammalian cochlea. This suggests a significant role for CGRP in efferent modulation of the output of this mechanosensory organ.