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The Journal of Neuroscience, March 15, 2003, 23(6):2141
Resting Potential and Submembrane Calcium Concentration of Inner
Hair Cells in the Isolated Mouse Cochlea Are Set by KCNQ-Type Potassium
Channels
Dominik
Oliver1,
Marlies
Knipper2,
Christian
Derst1, and
Bernd
Fakler1
1 Physiologisches Institut der Universität
Freiburg, 79104 Freiburg, Germany, and 2 Tübingen
Hearing Research Centre, Molecular Neurobiology, 72076 Tübingen,
Germany
Cochlear inner hair cells (IHCs) transduce sound-induced vibrations
into a receptor potential (RP) that controls afferent synaptic activity
and, consequently, frequency and timing of action potentials in the
postsynaptic auditory neurons. The RP is thought to be shaped by the
two voltage-dependent K+ conductances,
IK,f and
IK,s, that are carried by
large-conductance Ca2+- and voltage-dependent
K+ (BK)- and KV-type
K+ channels. Using whole-cell voltage-clamp
recordings in the acutely isolated mouse cochlea, we show that IHCs
display an additional K+ current that is active at
the resting membrane potential ( 72 mV) and deactivates on
hyperpolarization. It is potently blocked by the KCNQ-channel
blockers linopirdine and XE991 but is insensitive to tetraethylammonium
and 4-aminopyridine, which inhibit
IK,f and
IK,s, respectively. Single-cell PCR
and immunocytochemistry showed expression of the KCNQ4 subunit in IHCs.
In current-clamp experiments, block of the KCNQ current shifted the
resting membrane potential by ~7 to 65 mV and led to a significant
activation of BK channels. Using BK channels as an indicator for
submembrane intracellular Ca2+ concentration
([Ca2+]i), it is shown that the
shift in IHC resting potential observed after block of the KCNQ
channels leads to an increase in
[Ca2+]i to values  1
µM. In conclusion, KCNQ channels set the resting membrane
potential of IHCs in the isolated organ of Corti and thus maintain
[Ca2+]i at low levels. Destabilization
of the resting potential and increase in
[Ca2+]i, as may result from
impaired KCNQ4 function in IHCs, provide a novel explanation for the
progressive hearing loss (DFNA2) observed in patients with defective
KCNQ4 genes.
Key words:
KCNQ channels; intracellular
Ca2+; BK channels; progressive hearing loss; hereditary deafness (DFNA2); cochlea
Copyright © 2003 Society for Neuroscience 0270-6474/03/2362141-09$05.00/0
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