Abstract

Large-conductance voltage- and Ca²⁺-activated K⁺ channels (BK_Ca) are involved in shaping spiking patterns in many neurons. Less is known about their role in mammalian inner hair cells (IHCs), mechanosensory cells with unusually large BK_Ca currents. These currents may be involved in shaping the receptor potential, implying crucial importance for the properties of afferent auditory signals.

We addressed the function of BK_Ca by recording sound-induced responses of afferent auditory nerve (AN) fibers from mice with a targeted deletion of the pore-forming α-subunit of BK_Ca (BKα^−/−) and comparing these with voltage responses of current-clamped IHCs. BK_Ca-mediated currents in IHCs were selectively abolished in BKα^−/−, whereas cochlear physiology was essentially normal with respect to cochlear sensitivity and frequency tuning.

BKα^−/− AN fibers showed deteriorated precision of spike timing, measured as an increased variance of first spike latency in response to tone bursts. This impairment could be explained by a slowed voltage response in the presynaptic IHC resulting from the reduced K⁺ conductance in the absence of BK_Ca. Maximum spike rates of AN fibers were reduced nearly twofold in BKα^−/−, contrasting with increased voltage responses of IHCs. In addition to presynaptic changes, which may be secondary to a modest depolarization of BKα^−/− IHCs, this reduction in AN rates suggests a role of BK_Ca in postsynaptic AN neurons, which was supported by increased refractory periods.

In summary, our results indicate an essential role of IHC BK_Ca channels for precise timing of high-frequency cochlear signaling as well as a function of BK_Ca in the primary afferent neuron.