Transmitter release from Rana pipiens vestibular hair cells via mGluRs: a role for intracellular Ca(++) release.
The response of the semicircular canal (SCC) to the group I mGluR-selective agonist dihydroxyphenylglycine (DHPG; 300 microM) - facilitation of afferent discharge rate - was dose-dependently reduced by the phospholipase C inhibitor U-73122 (1-100 microM; IC(50): 22 microM), the smooth endoplasmic reticulum Ca(++) ATPase inhibitor thapsigargin (100 nM-3 microM; IC(50): 500 nM), and xestospongin C (100 pM-1 microM; IC(50): 11 nM), an inositol trisphosphate receptor (IP(3)R) antagonist. Ryanodine, a modulator of Ca(++)-induced Ca(++) release, biphasically facilitated, then suppressed this response (1 nM-1 mM; approximate IC(50): 50 microM). 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 microM; n=3) and the cyclic-ADP ribose antagonist 8-Br-cyclic-ADP ribose (1-10 microM; 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.
D000818:Animals; D001306:Auditory Pathways / Q000187:drug effects / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D004594:Electrophysiology; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D047028:Macrocyclic Compounds; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010080:Oxazoles / Q000494:pharmacology; D011894:Rana pipiens; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000502:physiology*; D012433:Ryanodine / Q000494:pharmacology; D012665:Semicircular Canals / Q000187:drug effects / Q000502:physiology; D019284:Thapsigargin / Q000494:pharmacology
D047028:Macrocyclic Compounds; D018377:Neurotransmitter Agents; D010080:Oxazoles; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; C108644:xestospongin A; D012433:Ryanodine; D008734:Methoxyhydroxyphenylglycol; D019284:Thapsigargin; C010117:3,4-dihydroxyphenylglycol