Dataset Information

Gemini encodes a zebrafish L-type calcium channel that localizes at sensory hair cell ribbon synapses.

ABSTRACT: L-type Ca2+ channels (LTCCs) drive the bulk of voltage-gated Ca2+ entry in vertebrate inner ear hair cells (HCs) and are essential for mammalian auditory processing. LTCC currents have been implicated in neurotransmitter release at the HC afferent active zone, the ribbon synapse. It is likely that LTCCs play a direct role in vesicle fusion; however, the subcellular localization of the channels in HCs has not been fully resolved. Via positional cloning, we show that mutations in a zebrafish LTCC encoding gene, cav1.3a, underlie the auditory-vestibular defects of gemini (gem) circler mutants. gem homozygous receptor mutant HCs display normal cell viability, afferent synaptogenesis, and peripheral innervation, yet exhibit strongly reduced extracellular potentials (approximately 50% of wild-type potentials). Apical FM1-43 uptake, however, is unaffected in gem mutant HCs, suggesting that mechanotransduction channels are functional. Using a Gem-specific antibody, we show that the bulk of Gem/Ca(v)1.3a immunoreactivity in HCs is restricted to basally located focal spots. The number and location of focal spots relative to nerve terminals, and their remarkable ring-shaped structure, which is reminiscent of synaptic dense bodies, are consistent with Gem/Ca(v)1.3a channels clustering at HC ribbon synapses.

SUBMITTER: Sidi S

PROVIDER: S-EPMC6729292 | biostudies-literature | 2004 Apr

REPOSITORIES: biostudies-literature

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gemini encodes a zebrafish L-type calcium channel that localizes at sensory hair cell ribbon synapses.

Sidi Samuel S Busch-Nentwich Elisabeth E Friedrich Rainer R Schoenberger Ulrike U Nicolson Teresa T

The Journal of neuroscience : the official journal of the Society for Neuroscience 20040401 17

L-type Ca2+ channels (LTCCs) drive the bulk of voltage-gated Ca2+ entry in vertebrate inner ear hair cells (HCs) and are essential for mammalian auditory processing. LTCC currents have been implicated in neurotransmitter release at the HC afferent active zone, the ribbon synapse. It is likely that LTCCs play a direct role in vesicle fusion; however, the subcellular localization of the channels in HCs has not been fully resolved. Via positional cloning, we show that mutations in a zebrafish LTCC ...[more]

PMID: 15115817

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Project description:Key pointsThe present study aimed to determine the sensory adaptation characteristics of hair cell ribbon synapses in vivo. Hair cells of the zebrafish lateral line transmit hydrodynamic stimuli to the posterior lateral line ganglion afferent neurons. Excitatory hair bundle deflections by water-jet stimuli cause glutamate release at hair cell synapses with a rapid (phasic) and a sustained component, which are likely linked to the exocytosis of distinct vesicle pools. The glutamate-induced increase in afferent neuron firing rate adapts over time, which is mirrored by the depression of neurotransmitter release, without preventing phase-locking. Adaptation also occurs during inhibitory hair bundle displacements, highlighting a shift in the sensitivity range of the lateral line during prolonged stimulation. Postsynaptic mechanisms exert some degree of regulation on the afferent firing adaptation. We conclude that vesicle depletion is the primary determinant of firing rate adaptation, allowing lateral line hair cell ribbon synapses to maintain sensitivity to sustained stimuli.AbstractAdaptation is used by sensory systems to adjust continuously their sensitivity to match changes in environmental stimuli. In the auditory and vestibular systems, the release properties of glutamate-containing vesicles at the hair cell ribbon synapses play a crucial role in sensory adaptation, thus shaping the neural response to sustained stimulation. How ribbon synapses regulate the release of glutamate and how they modulate afferent responses in vivo is still largely unknown. Here, we have used two-photon imaging and electrophysiology to investigate the synaptic transfer characteristics of the hair cells in the context of sensory adaptation in live zebrafish. Prolonged and repeated water-jet stimulation of the hair cell stereociliary bundles caused adaptation of the action potential firing rate elicited in the afferent neurons. By monitoring glutamate at ribbon synapses using time-lapse imaging, we identified two kinetically distinct release components: a rapid response that was exhausted within 50-100 ms and a slower and sustained response lasting the entire stimulation. After repeated stimulations, the recovery of the fast component followed a biphasic time course. Depression of glutamate release was largely responsible for the rapid firing rate adaptation recorded in the afferent neurons. However, postsynaptic Ca2+ responses had a slower recovery time course compared to that of glutamate release, indicating that they are likely to contribute to the afferent firing adaptation. Hair cells also exhibited a form of adaptation during inhibitory bundle stimulations. We conclude that hair cells have optimised their synaptic machinery to encode prolonged stimuli and to maintain their sensitivity to new incoming stimuli.

Project description:Retinal bipolar cells (BCs) compose the canonical vertical excitatory pathway that conveys photoreceptor output to inner retinal neurons. Although synaptic transmission from BC terminals is thought to rely almost exclusively on Ca2+ influx through voltage-gated Ca2+ (CaV) channels mediating L-type currents, the molecular identity of CaV channels in BCs is uncertain. Therefore, we combined molecular and functional analyses to determine the expression profiles of CaV α1, β, and α2δ subunits in mouse rod bipolar (RB) cells, BCs from which the dynamics of synaptic transmission are relatively well-characterized. We found significant heterogeneity in CaV subunit expression within the RB population from mice of either sex, and significantly, we discovered that transmission from RB synapses was mediated by Ca2+ influx through P/Q-type (CaV2.1) and N-type (CaV2.2) conductances as well as the previously-described L-type (CaV1) and T-type (CaV3) conductances. Furthermore, we found both CaV1.3 and CaV1.4 proteins located near presynaptic ribbon-type active zones in RB axon terminals, indicating that the L-type conductance is mediated by multiple CaV1 subtypes. Similarly, CaV3 α1, β, and α2δ subunits also appear to obey a "multisubtype" rule, i.e., we observed a combination of multiple subtypes, rather than a single subtype as previously thought, for each CaV subunit in individual cells.SIGNIFICANCE STATEMENT Bipolar cells (BCs) transmit photoreceptor output to inner retinal neurons. Although synaptic transmission from BC terminals is thought to rely almost exclusively on Ca2+ influx through L-type voltage-gated Ca2+ (CaV) channels, the molecular identity of CaV channels in BCs is uncertain. Here, we report unexpectedly high molecular diversity of CaV subunits in BCs. Transmission from rod bipolar (RB) cell synapses can be mediated by Ca2+ influx through P/Q-type (CaV2.1) and N-type (CaV2.2) conductances as well as the previously-described L-type (CaV1) and T-type (CaV3) conductances. Furthermore, CaV1, CaV3, β, and α2δ subunits appear to obey a "multisubtype" rule, i.e., a combination of multiple subtypes for each subunit in individual cells, rather than a single subtype as previously thought.

Dataset Information

Gemini encodes a zebrafish L-type calcium channel that localizes at sensory hair cell ribbon synapses.

Publications

gemini encodes a zebrafish L-type calcium channel that localizes at sensory hair cell ribbon synapses.

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