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In the cochlea, the endolymph is a unique
extra-cellular fluid containing high contration of K+
(150 mM). This high concentration K+ results from
an active secretion of K+ by the stria vascularis
into the scala media (Figure 1). The K+ flux generates
a 80 mV DC potential called endocochlear potential which can
be recorded in the scala media and that is crucial for mecanotransduction
by the hair cells.
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Figure
1: Schematic showing ions movements in the stria vascularis.
Potassium ions
coming from the spiral ligament penetrate the basal
cells of the stria vascularis
through a network
of gap junctions. This ion then reaches the intermediate
cells (melanocytes) which secrete the potassium in the
intrastrial space through potassium channels Kir4.1
and Merg1a. The endocochlear potential is generated
across the intermediate cells membrane. The intrastrial
space has a low concentration of potassium and a high
concentration of sodium. This low potassium concentration
is necessary to facilitate the transfer of this ion
from the intermediate cells (membrane potential - 110
mV) to the intrastrial space. Potassium ions are pumped
into the marginal cells by the Na,K-ATPase and the co-transporter
NKCC1. Finally, the potassium is extruded into the scala
media through KCNQ1/KCNE1 potassium channels. |
The Na,K-ATPase is a key protein in the endolymph
homeostasis, mainly expressed in the SV. We recently demonstrated
that FXYD6 which is also strongly expressed in the SV (Figure
2) was an auxiliary protein able to control, in association
with the Na,K-ATPase, the endolymph electrochemical equilibrium
(Figure 3) (Delprat et al., 2007).
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Figure 2 : Expression
of FXYD6 in the rat cochlea by immunohistochemistry.
The antibody detects the protein (green) into deiters
cells (D) ; outer sulcus cells (OSC) ; interdental cells
(IC) ; supralimbal fibrocytes (FS) ; stria vascularis
(SV). The fibers and the soma of the primary auditory
neurons are labelled. Hair cells as well as soma of
the primary auditory neurons are detected using a parvalbumin
antibody (red). |
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Figure 3 : Effects
of FXYD6 on the transport properties of Na,K-ATPase.
(A) K1/2 K+ values of
Na,K-ATPase a1-b2
complexes in the absence (closed circles) or presence
(open circles) of FXYD6. *p<0.05 (B) K1/2
Na+ values of Na,K-ATPase a1-b2
complexes in the absence or presence of FXYD6. ***p<
0.001. |
Our team works at deciphering the molecular
mechanisms implicated in the production and regulation of
the electrochemical composition of the endolymph composition
by the stria vacularis. We are focusing onto the partners
of the K+ channels (KCNQ1/KCNE1, KCNJ10) and Na,K-ATPase.
Selected recent references:
Delprat B, Schaer D, Roy S, Wang J, Puel JL, Gerring
K. FXYD6 is a novel regulator of Na,K-ATPase expressed
in the inner ear. J. Biol. Chem. 2007, 282: 7450-7456.
Delprat B, Ruel J, Guitton M, Hamard G, Lenoir M,
Pujol R, Puel JL, Brabet P, Hamel CP. Deafness and
cochlear fibrocyte alterations in mice deficient for the inner
ear protein otospiralin. Mol. Cell. Biol. 2005, 25: 847-853.
Lavigne-Rebillard M, Delprat B, Surget M-O, griffoin
J-M, Weil D, Arbones M, Vincent R, Hamel CP. Gene
structure, chromosomal localisation and mutation screening
of the human gene for the inner ear protein Otospiralin. Neurogenetics
2003, 4: 137-140.
Delprat B, Boulanger A, Wang J, Beaudoin V, Guitton M, Ventéo
S, Dechesne C, Lavigne-rebillard M, Puel J-L, Hamel C.
Down regulation of Otospiralin, a novel inner ear protein,
causes hair cell degeneration and deafness. J. Neurosci. 2002,
22: 1718-1725.
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