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 vestibular afferent fibers. Application of 1-10 mM caffeine to hair cells potentiated Ca2+ responses evoked by depolarization at selected Ca2+ hotspots, and also induced a graded increase in celi membrane capacitance (deltaCm), signaling exocytosis of transmìtter. Ca2+ signals evoked by caffeine peaked in a region located about 10 microm from the base of the hair cell. Similarly localized [Ca2+]i increases were observed following 500 ms depolarizations, but not with 50 ms depolarizations, suggesting the occurrence of calcium-induced calcium release (CICR) from the same stores. Both [Ca]i and deltaCm responses were inhibited following incubation wìth ryanodine (40 microM) 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 (APs) and of excitatory postsynaptic potentials (EPSP). Neither caffeine nor ryanodine affected the shape and amplitude of miniature EPSP (mEPSP), 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.
Presynaptic Calcium Stores Modulate Afferent Release in Vestibular Hair Cells
MARTINI, Marta;ROSSI, Marialisa
2003
Abstract
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 vestibular afferent fibers. Application of 1-10 mM caffeine to hair cells potentiated Ca2+ responses evoked by depolarization at selected Ca2+ hotspots, and also induced a graded increase in celi membrane capacitance (deltaCm), signaling exocytosis of transmìtter. Ca2+ signals evoked by caffeine peaked in a region located about 10 microm from the base of the hair cell. Similarly localized [Ca2+]i increases were observed following 500 ms depolarizations, but not with 50 ms depolarizations, suggesting the occurrence of calcium-induced calcium release (CICR) from the same stores. Both [Ca]i and deltaCm responses were inhibited following incubation wìth ryanodine (40 microM) 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 (APs) and of excitatory postsynaptic potentials (EPSP). Neither caffeine nor ryanodine affected the shape and amplitude of miniature EPSP (mEPSP), 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.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.