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The physiological properties of the inner hair cells relies upon the relationship between stimulation and the secretion of the neurotransmitter at the level of the synapse with the endbulbs of the auditory nerve. The molecular mechanisms of this synapse are detailed here.
Relationship between stimulation and secretion
The depolarisation of the hair cells (IHCs) causes L-type voltage-sensitive calcium channels located near the regions of afferent synapses to open. Each active region in characterised by the presence of an electron-dense structure called a synaptic ribbon. This synaptic ribbon is anchored to the plasma membrane and surrounded by synaptic vesicles which contain glutamate, the IHC neurotransmitter.
There is one ribbon per active region and ten to twenty active regions per IHC.
Each active region synapses with a dendrite from a single fibre from the auditory nerve. This means that 10 to 20 type I spiral ganglion neurons connect to one IHC.
S. Blatrix, d'après R. Nouvian
- Hair cell synapses are equipped with an unconventional organelle: the synaptic ribbon. The latter is surrounded by a layer of synaptic vesicles and is anchored to the membrane by the protein "Bassoon".
- The protein "RIBEYE" is the major component of synaptic ribbons.
- The vesicular transporter "VGLUT3" ensures that the synaptic vesicles are filled with glutamate. Otoferlin is the calcium detector used for exocytosis.
- In responses to a sound stimulus, the stretch-sensitive channels open.
- The influx of endolymphatic potassium depolarises the IHCs.
- Voltage-senstive calcium channels open, which causes an influx of calcium close to the ribbons.
- Fixation of calcium on the Otofelin C2 domains causes the synaptic vesicles to fuse with the plasma membrane.
- Glutamate, released into the synaptic cleft, activates the AMPA glutamate receptors in the afferent nerve fibres.
- The nerve signal is transported to the cochlear nucleus.
Information transfer at the first auditory synapse is essential for the transmission of acoustic information to higher centres. The crucial role of this step is also reflected by hearing losses that arise from a problem in the IHC ribbon synapse:
- A mutation in the gene which codes for the Cav1.3 subunit, responsible for in the calcium influx into the IHC, is the cause of a hearing loss related to bradycardia.
- Harmonin, which has been implicated in Usher syndrome 1C (loss of both vision and hearing), regulates the distribution of calcium channels along the plasma membrane.
- Otoferlin, which is the calcium detector for exocytosis and required for the replenishment of the vesicles in the active regions, is responsible for DFNB9 non-syndromic hearing loss.
- A mutation in VGLUT3, the glutamate vesicular transporter, causes DFNA25 nonsyndromic hearing loss.
- A mutation in CABP2, which regulates the activity of the calcium channels, provokes DFNB93 non-syndromic hearing loss.