Contribution of BK Ca2+-activated K+ channels to auditory neurotransmission in the Guinea pig cochlea.
Journal of Neurophysiology. 2003-07-01; 90(1): 320-332
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1. J Neurophysiol. 2003 Jul;90(1):320-32. Epub 2003 Feb 12.
Contribution of BK Ca2+-activated K+ channels to auditory neurotransmission in
the Guinea pig cochlea.
Skinner LJ(1), Enée V, Beurg M, Jung HH, Ryan AF, Hafidi A, Aran JM, Dulon D.
(1)Laboratoire de Biologie Cellulaire et Moléculaire de l’Audition, Equipe Mixte
Institut National de la Santé et de la Recherche Médicale 99-27, Université de
Bordeaux 2, Centre Hospitalier Universitaire Hôpital Pellegrin, 33076 Bordeaux,
Large-conductance calcium-activated potassium (BK) channels are known to play a
prominent role in the hair cell function of lower vertebrates where these
channels determine electrical tuning and regulation of neurotransmitter release.
Very little is known, by contrast, about the role of BK channels in the mammalian
cochlea. In the current study, we perfused specific toxins in the guinea pig
cochlea to characterize the role of BK channels in cochlear neurotransmission.
Intracochlear perfusion of charybdotoxin (ChTX) or iberiotoxin (IbTX) reversibly
reduced the compound action potential (CAP) of the auditory nerve within minutes.
The cochlear microphonics (CM at f1 = 8 kHz and f2 = 9.68 kHz) and their
distortion product (DPCM at 2f1-f2) were essentially not affected, suggesting
that the BK specific toxins do not alter the active cochlear amplification at the
outer hair cells (OHCs). We also tested the effects of these toxins on the whole
cell voltage-dependent membrane current of isolated guinea pig inner hair cells
(IHCs). ChTX and IbTX reversibly reduced a fast outward current (activating above
-40 mV, peaking at 0 mV with a mean activation time constant tau ranging between
0.5 and 1 ms). A similar block of a fast outward current was also observed with
the extracellular application of barium ions, which we believe permeate through
Ca2+ channels and block BK channels. In situ hybridization of Slo antisense
riboprobes and immunocytochemistry demonstrated a strong expression of BK
channels in IHCs and spiral ganglion and to a lesser extent in OHCs. Overall, our
results clearly revealed the importance of BK channels in mammalian cochlear
neurotransmission and demonstrated that at the presynaptic level, fast BK
channels are a significant component of the repolarizing current of IHCs.
PMID: 12611976 [Indexed for MEDLINE]