Ryanodine receptors and BK channels act as a presynaptic depressor of neurotransmission in cochlear inner hair cells.
European Journal of Neuroscience. 2005-09-01; 22(5): 1109-1119
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1. Eur J Neurosci. 2005 Sep;22(5):1109-19.
Ryanodine receptors and BK channels act as a presynaptic depressor of
neurotransmission in cochlear inner hair cells.
Beurg M(1), Hafidi A, Skinner LJ, Ruel J, Nouvian R, Henaff M, Puel JL, Aran JM,
(1)Laboratoire de Biologie Cellulaire et Moléculaire de l’Audition, EA 3665
Université Victor Segalen Bordeaux 2, CHU Hôpital Pellegrin, 33076 Bordeaux,
Ryanodine receptors (RyRs) are known to contribute to the regulation of free
cytosolic calcium concentration. This family of intracellular calcium channels
plays a significant role in calcium-induced-calcium-release (CICR), and have been
implicated in calcium-dependent processes requiring exquisite spatio-temporal
regulation. In order to characterize the importance of these intracellular
calcium channels in cochlear physiology, we perfused the guinea pig cochlea with
antagonistic concentrations of ryanodine. The distortion products of the cochlear
microphonic and the compound action potential of the auditory nerve were
reversibly inhibited by ryanodine (IC(50)=27.3 microm, Hill coefficient=1.9),
indicating an action at the cochlear amplifier. Single auditory nerve fibre
recordings showed that ryanodine slightly increased spontaneous firing rates by
22%, suggesting an excitatory effect of ryanodine. This paradoxical effect could
be explained by an inhibitory action of ryanodine on presynaptic BK channels of
inner hair cells (IHC). Indeed, perfusing iberiotoxin also increased the
spontaneous firing activity of the auditory nerve fibres. Furthermore, whole-cell
patch-clamp recordings demonstrated that ryanodine inhibits BK currents at the
IHC level. Conversely, immunohistochemistry demonstrated a strong expression of
RyR in IHCs and, more particularly, below the cuticular plate where membranous BK
channels are highly expressed. Overall, the study demonstrated a key role for RyR
and CICR in signal transduction at the IHCs. We therefore propose that coupled
RyR–BK channels act to suppress the fast neurotransmission in IHCs.
PMID: 16176352 [Indexed for MEDLINE]