Fast recovery of disrupted tip links induced by mechanical displacement of hair bundles
Résumé
Hearing and balance rely on the capacity of mechanically sensitive
hair bundles to transduce vibrations into electrical signals that are
forwarded to the brain. Hair bundles possess tip links that interconnect
the mechanosensitive stereocilia and convey force to the transduction
channels. A dimer of dimers, each of these links comprises
two molecules of protocadherin 15 (PCDH15) joined to two of
cadherin 23 (CDH23). The “handshake” that conjoins the four molecules
can be disrupted in vivo by intense stimulation and in vitro by
exposure to Ca2+ chelators. Using hair bundles from the rat’s cochlea
and the bullfrog’s sacculus, we observed that extensive recovery of
mechanoelectrical transduction, hair bundle stiffness, and spontaneous
bundle oscillation can occur within seconds after Ca2+ chelation,
especially if hair bundles are deflected toward their short edges. Investigating
the phenomenon in a two-compartment ionic environment
that mimics natural conditions, we combined iontophoretic
application of a Ca2+ chelator to selectively disrupt the tip links of
individual frog hair bundles with displacement clamping to control
hair bundle motion and measure forces. Our observations suggest
that, after the normal Ca2+ concentration has been restored, mechanical
stimulation facilitates the reconstitution of functional tip links.
Origine : Publication financée par une institution