In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 23, No. 6 ( 2003-03-15), p. 2141-2149
Abstract:
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, I K,f and I K,s , that are carried by large-conductance Ca 2+ - and voltage-dependent K + (BK)- and K V -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 I K,f and I K,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 Ca 2+ concentration ([Ca 2+ ] i ), it is shown that the shift in IHC resting potential observed after block of the KCNQ channels leads to an increase in [Ca 2+ ] i to values ≥1 μ m . In conclusion, KCNQ channels set the resting membrane potential of IHCs in the isolated organ of Corti and thus maintain [Ca 2+ ] i at low levels. Destabilization of the resting potential and increase in [Ca 2+ ] 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.
Type of Medium:
Online Resource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.23-06-02141.2003
Language:
English
Publisher:
Society for Neuroscience
Publication Date:
2003
detail.hit.zdb_id:
1475274-8
SSG:
12
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