Hannah Martin

Figure 1. A. The cartoon depicts four cell types in the vestibular epithelium: type I and II hair cells, afferent neurons, and efferent neurons. B. Whole-cell voltage-clamp recordings from type I and II hair cells illustrate their step-elicited potassium conductances gKL and gK. C. Boltzmann fits of conductance at the “tail” end of the test step (*) reveal differences in size (Gmax) and voltage dependence (V1/2) of these potassium currents. Error bars are SEM

In type I and II vestibular hair cells, different voltage-dependent K+ currents shape the signal as it propagates from the mechanoelectrical transduction channels (TMCs) at the tip of the HC bundle to spiking in the post-synaptic afferent neuron. The differences are evident in whole-cell currents recorded from hair cells in response to the same voltage protocol (Fig 1b). Type I hair cells have a low-voltage-activated conductance, gK,L, that is open at resting potential (indicated by dotted line at -64mV in the bottom voltage protocol), while the K+ conductance in type II hair cells (gK) activates positive to resting potential. The tail conductance (*) contains information about voltage dependence and size of these potassium currents. In Fig 1c, gK,L activates 50mV negative to gK and has a maximum conductance on average 6 times greater than that of gK. In this way, by lowering input resistance, gK,L reduces the charging time of the membrane, allowing the receptor potential to better follow high frequency stimuli. The open gK,L channels also pass current directly to the postsynaptic afferent terminal in an unusual and fast form of non-quantal synaptic transmission (Songer & Eatock 2013; Contini et al. 2017). 

The molecular identity of gK,L remains unsettled; suggestions have included KV7.4 (KCNQ4; Kharkovets et al. 2000; Holt et al. 2007) and KV11.3 (erg3; Hurley et al. 2006). Other channels contribute to non-quantal transmission and potential modulate gKL, particularly KCa1.1 (BK; Contini et al. 2020). Consistent with sensitivity to second messengers, gK,L’s properties change with time during whole-cell recordings and under the influence of protein kinase inhibitors (Hurley et al. 2006) and nitric oxide donors (Chen and Eatock 2000). We are interested in whether stimulus history or efferent feedback can regulate gK,L to alter the gain and frequency dependence of the afferent signal.

Literature Cited

Chen, JWY, & Eatock, RA (2000). Major potassium conductance in type I hair cells from rat semicircular canals: Characterization and modulation by nitric oxide. Journal of Neurophysiology, 84(1), 139–151.

Contini, D, Price, SD, & Art, JJ (2017). Accumulation of K+ in the synaptic cleft modulates activity by influencing both vestibular hair cell and calyx afferent in the turtle. Journal of Physiology, 595(3), 777–803.

Contini, D, Holstein, G, Art, JJ (2020). Synaptic cleft microenvironment influences potassium permeation and synaptic transmission in hair cells surrounded by calyx afferents in the turtle. Journal of Physiology, 598(4), 853-889.

Holt, JR, Stauffer, EA, Abraham, D, & Géléoc, GSG (2007). Dominant-negative inhibition of M-like potassium conductances in hair cells of the mouse inner ear. Journal of Neuroscience, 27(33), 8940–8951.

Hurley, KM, Gaboyard, S, Zhong, M, Price, SD, Wooltorton, JRA, Lysakowski, A, & Eatock, RA (2006). M-like K+ currents in type I hair cells and calyx afferent endings of the developing rat utricle. Journal of Neuroscience, 26(40), 10253–10269.

Kharkovets, T, Hardelin, JP, Safieddine, S, Schweizer, M, El-Amraoui, A, Petit, C, & Jentsch, TJ (2000). KCNQ4, a K+ channel mutated in a form of dominant deafness, is expressed in the inner ear and the central auditory pathway. PNAS, 97(8), 4333–4338.

Songer, JE, & Eatock, RA (2013). Tuning and timing in mammalian type I hair cells and calyceal synapses. Journal of Neuroscience, 33(8), 3706–3724.