Influence of atp and atp agonists on the physiology of the isolated semicircular canal of the frog ( Rana Pipiens)

Abstract

In the present study, the influence of extracellular ATP and ATP agonists in the physiology of the vestibular organs was examined, using the in vitro model of the isolated semicircular canal of the frog ( Rana pipiens). The firing activity of the afferent nerve, the d.c. nerve potential and the transepithelial potential were measured in the absence and presence of mechanical stimulation of the sensory epithelium. Administration of ATP into the perilymphatic compartment, from 10 −12 to 10 −3M, increased the firing rate of the afferent fibers recorded in the absence of mechanical stimulation. Recordings of the d.c. nerve potential indicated that the afferent fibers were hyperpolarized. The presence of the purine also modified the transepithelial potential. During mechanical stimulation of the sensory epithelium, both the evoked afferent firing and the evoked variation of the d.c. nerve potential were reduced in the presence of ATP. However, ATP did not effect the evoked modulation of the transepithelial potential, evoked by the mechanical stimulation. Administration of the P 2x purinoceptor agonists, α,β-methylene-ATP and β, γ-methylene-ATP, at concentrations between 10 −12 and 10 −3 M, did not significantly modify the different bioelectrical activities investigated. In contrast, 2-methylthio-ATP, a P 2y purinoceptor agonist, more potent and efficacious than ATP in its effect on the spontaneous firing. Concurrently, no modification of the d.c. nerve potential, the transepithelial potential and their variation during mechanical stimulation was observed. In opposition to the ATP effect, the total amplitude of the evoked firing was increased in the presence of 2-methylthio-ATP. These data suggest that extracellular ATP, present in the perilymphatic compartment, may act as a neuromodulator in the vestibular physiology. The effects of the purine appear to be mediated by the activation of a P 2y subtype of purinoceptor. The absence of an effect of ATP and 2-methylthio-ATP on the evoked variation of the transepithelial potential suggest that the purine did not affect the processes responsible for the generation of the receptor potential but more likely modified the mechanisms involved in the release of the neurotransmitter from the hair cells and/or acted on the afferent endings.