TY - JOUR T1 - Presynaptic Calcium Stores Modulate Afferent Release in Vestibular Hair Cells JF - The Journal of Neuroscience JO - J. Neurosci. SP - 6894 LP - 6903 DO - 10.1523/JNEUROSCI.23-17-06894.2003 VL - 23 IS - 17 AU - Andrea Lelli AU - Paola Perin AU - Marta Martini AU - Catalin D. Ciubotaru AU - Ivo Prigioni AU - Paolo Valli AU - Maria L. Rossi AU - Fabio Mammano Y1 - 2003/07/30 UR - http://www.jneurosci.org/content/23/17/6894.abstract N2 - Hair cells, the mechanoreceptors of the acoustic and vestibular system, are presynaptic to primary afferent neurons of the eighth nerve and excite neural activity by the release of glutamate. In the present work, the role played by intracellular Ca2+ stores in afferent transmission was investigated, at the presynaptic level, by monitoring changes in the intracellular Ca2+ concentration ([Ca2+]i) in vestibular hair cells, and, at the postsynaptic level, by recording from single posterior canal afferent fibers. Application of 1-10 mm caffeine to hair cells potentiated Ca2+ responses evoked by depolarization at selected Ca2+ hot spots, and also induced a graded increase in cell membrane capacitance (ΔCm), signaling exocytosis of the transmitter. Ca2+ signals evoked by caffeine peaked in a region located ∼10 μm from the base of the hair cell. [Ca2+]i increases, similarly localized, were observed after 500 msec depolarizations, but not with 50 msec depolarizations, suggesting the occurrence of calcium-induced calcium release (CICR) from the same stores. Both Ca2+ and ΔCm responses were inhibited after incubation with ryanodine (40 μm) for 8-10 min. Consistent with these results, afferent transmission was potentiated by caffeine and inhibited by ryanodine both at the level of action potentials and of miniature EPSPs (mEPSPs). Neither caffeine nor ryanodine affected the shape and amplitude of mEPSPs, indicating that both drugs acted at the presynaptic level. These results strongly suggest that endogenous modulators of the CICR process will affect afferent activity elicited by mechanical stimuli in the physiological frequency range. ER -