Excitatory GABAergic modulation of calyx terminals in the vestibular sensory end organ

GABAergic sources have been identified in the vestibular sensory neuroepithelium, mainly in the supporting cells. However, existence of GABA receptors or any possible GABAergic effects on vestibular nerve afferents has not been investigated. The current study was conducted to determine whether activation of GABAB receptors affects calyx afferent terminals in the central region of the cristae of the semicircular canals in rats. We used patch clamp recording in P13 to P18 Sprague Dawley rats of either sex. Application of GABA-B receptor agonist baclofen inhibited voltage activated outward potassium currents. This effect was blocked by selective GABAB receptor antagonist CGP 35348. Antagonists of small (SK) and large (BK) current potassium channels resulted in an almost complete block of baclofen effect. The remaining baclofen effect was due to inhibition of voltage gated calcium channels and was blocked by cadmium chloride. Furthermore, baclofen had no effect in the absence of calcium in the extracellular fluid. Inhibition of potassium currents by GABAB activation resulted in an excitatory effect on calyx terminal action potential firing. While in the control condition calyces could only fire a single action potential during step depolarizations, in the presence of baclofen they fired continuously during steps and a few even showed spontaneous discharge. We also found a decrease in threshold for action potential generation and a decrease in first spike latency during step depolarization. These results provide the first evidence for the presence of GABAB receptors on calyx terminals, show that their activation results in an unusual excitatory effect and that GABA inputs could be used to modulate calyx response properties.