Transmitter release from Rana pipiens vestibular hair cells via mGluRs: A role for intracellular Ca ++ release

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The response of the semicircular canal (SCC) to the group I mGluR-selective agonist dihydroxyphenylglycine (DHPG; 300 μM) – facilitation of afferent discharge rate – was dose-dependently reduced by the phospholipase C inhibitor U-73122 (1–100 μM; IC 50: 22 μM), the smooth endoplasmic reticulum Ca ++ ATPase inhibitor thapsigargin (100 nM–3 μM; IC 50: 500 nM), and xestospongin C (100 pM–1 μM; IC 50: 11 nM), an inositol trisphosphate receptor (IP 3R) antagonist. Ryanodine, a modulator of Ca ++-induced Ca ++ release, biphasically facilitated, then suppressed this response (1 nM–1 mM; approximate IC 50: 50 μM). 5 mM caffeine increased the amplitude (34.6±13.4%) and duration (453±169.8%; n=4) of the response of the SCC to DHPG, while 50 mM caffeine eliminated this response ( n=2). The protein kinase C inhibitor bisindolylmaleimide I-HCl (10–100 μM; n=3) and the cyclic-ADP ribose antagonist 8-Br-cyclic-ADP ribose (1–10 μM; n=3) had no effect on the response of the SCC to DHPG. These data suggest that the increase in transmitter release following activation of group I mGluRs on vestibular hair cells is associated with intracellular Ca ++ release from both IP 3-sensitive and ryanodine/caffeine-sensitive intracellular Ca ++ stores. Such positive feedback on transmitter release may serve to enhance the contrast between the spontaneous and stimulus-evoked modes of hair cell transmitter release, thereby optimizing signal discrimination at the synapse between hair cells and vestibular afferent fibers.