KV1.8 (Kcna10) potassium channels enhance fast, linear signaling in vestibular hair cells and facilitate vestibulomotor reflexes and balance

Abstract

Vestibular hair cells (HCs) faithfully and rapidly detect head motions and gravity, driving motor reflexes that stabilize balance and gaze during locomotion. With the transition from water to land, the amniote vestibular inner ear added type I HCs, which differ from amniote type II HCs and anamniote HCs by their large calyx afferent synapse, non-quantal afferent transmission, and a large, low-voltage-activated K+ conductance (gK,L). We recently showed that both gK,L and the major type II K+ conductances (A-type and delayed rectifier) require KV1.8 (Kcna10) subunits. Here we compared KV1.8-null (Kcna10-/-) and control animals to see how KV1.8 affects function as measured by receptor potentials and nonquantal postsynaptic potentials evoked by direct hair bundle motions, and by vestibulomotor behaviors. Recordings were taken from extrastriolar zones of the utricle. In both HC types, KV1.8 affected receptor potentials by reducing response time and gain, increasing dampening, and expanding the frequency bandwidth toward high frequencies. Effects are most prominent in type I HCs: lowpass corner frequencies of receptor potentials in Kcna10-/- HCs of both types were [~]20 Hz, vs. [~]400 Hz in control type I and [~]70 Hz in control type II. We recorded nonquantal postsynaptic potentials from extrastriolar calyces, and found that the synaptic transfer function had lower gain and greater phase lag in Kcna10-/- mice. In behavioral tests, Kcna10-/- mice had vestibular-ocular reflexes with different response dynamics at low frequencies, impaired performance on a narrow balance beam, abnormal body posture and abnormal head motions in water and on land, and also rarely assumed bipedal stances. These vestibulomotor deficits in Kcna10-/- mice likely reflect the changes noted in HCs, where KV1.8 expression is concentrated; that is, slower signaling of high-frequency head motions by Kcna10-/- HCs fails to fully stabilize body and head position during locomotion. Thus, gK,L (KV1.8) contributes to fast signal transmission in the amniote vestibular inner ear and supports improved performance on challenging vestibulomotor tasks. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=191 SRC="FIGDIR/small/634388v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@126570borg.highwire.dtl.DTLVardef@1cab5borg.highwire.dtl.DTLVardef@36240corg.highwire.dtl.DTLVardef@789617_HPS_FORMAT_FIGEXP M_FIG C_FIG