Contribution of BK Ca2+-activated K+ channels to auditory neurotransmission in the Guinea pig cochlea.
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.
Skinner
Liam J
LJ
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, France.
Enée
Veronique
V
Beurg
Maryline
M
Jung
Hak Hyun
HH
Ryan
Allen F
AF
Hafidi
Aziz
A
Aran
Jean-Marie
JM
Dulon
Didier
D
D000161:Acoustic Stimulation; D000200:Action Potentials; D000818:Animals; D018999:Charybdotoxin / Q000494:pharmacology; D003051:Cochlea / Q000737:chemistry* / Q000502:physiology*; D003056:Cochlear Nerve / Q000502:physiology*; D004594:Electrophysiology; D005260:Female; D006168:Guinea Pigs; D006199:Hair Cells, Auditory, Inner / Q000737:chemistry*; D006309:Hearing / Q000502:physiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008564:Membrane Potentials; D009498:Neurotoxins / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000032:analysis* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012533:Scala Tympani / Q000502:physiology; D009435:Synaptic Transmission
D051036:Large-Conductance Calcium-Activated Potassium Channels; D009498:Neurotoxins; D010455:Peptides; D024681:Potassium Channels, Calcium-Activated; D018999:Charybdotoxin; C064719:iberiotoxin