Avtor/Urednik     Pangršič, Tina; Lasarow, Livia; Reuter, Kirsten; Takago, Hideki
Naslov     Hearing requires otoferlin-dependent efficient replenishment of synaptic vesicles in hair cells
Tip     članek
Vir     Nat Neurosci
Vol. in št.     Letnik 13, št. 7
Leto izdaje     2010
Obseg     str. 869-76
Jezik     eng
Abstrakt     Inner hair cell ribbon synapses indefatigably transmit acoustic information. The proteins mediating their fast vesicle replenishment (hundreds of vesicles per s) are unknown. We found that an aspartate to glycine substitution in the C2F domain of the synaptic vesicle protein otoferlin impaired hearing by reducing vesicle replenishment in the pachanga mouse model of human deafness DFNB9. In vitro estimates of vesicle docking, the readily releasable vesicle pool (RRP), Ca2+ signaling and vesicle fusion were normal. Moreover, we observed postsynaptic excitatory currents of variable size and spike generation. However, mutant active zones replenished vesicles at lower rates than wild-type ones and sound-evoked spiking in auditory neurons was sparse and only partially improved during longer interstimulus intervals. We conclude that replenishment does not match the release of vesicles at mutant active zones in vivo and a sufficient standing RRP therefore cannot be maintained. We propose that otoferlin is involved in replenishing synaptic vesicles.
Deskriptorji     HAIR CELLS, INNER
AUDITORY PERCEPTION
SPIRAL GANGLION
ACOUSTIC STIMULATION
SYNAPTIC VESICLES
CALCIUM
EXOCYTOSIS
DEAFNESS
SYNAPTIC TRANSMISSION
PATCH-CLAMP TECHNIQUES
NEUROTRANSMITTERS
DISEASE MODELS, ANIMAL
MICE, INBRED STRAINS