Eps8 is necessary for the normal expression of cochlear, but not vestibular hair cell K+ channels

Epidermal growth factor receptor pathway substrate 8 (Eps8) is an evolutionarily conserved signal transducer endowed with multiple functions in the control of actin dynamics and in the integration of these events with other receptor-activated signaling pathways. We have recently shown that Eps8 knockout (KO) mice are deaf and that the normal development of cochlear hair cells stereocilia and ion channels is prevented [1]. More specifically, IK,n, a low voltageactivated K+ current which appears at around hearing threshold, was absent. Curiously, though Eps8 is also expressed in vestibular hair cells [2], no gross vestibular defects have been reported in Eps8 KO mice. However, mild vestibular defects can be hard to identify in rodents, and therefore we investigated if ion channel expression is altered in Eps8 KO mouse vestibular hair cells. Patch-clamp whole-cell recordings were obtained from in situ vestibular Type I hair cells from control and KO mice of 7 to 19 post-natal days. At this developmental stage vestibular hair cells normally express the mature-like variety of ion channels. We were particularly interested in IK,L, a low-voltage activated K+ current which, similar to IK,n in cochlear hair cells, is expressed late during development by vestibular Type I hair cells. Though IK,n and IK,L show different kinetics and pharmacology [3], and are presumably conducted through different ion channels, because of their negative voltage range of activation they are responsible for the cell low input resistance at rest. Here, we found that IK,L was normally present in Type I hair cells of Eps8 KO mice (n = 12). Furthermore, no major differences in macroscopic current amplitude and time course were observed between control and KO mice. These results indicate that, at difference from cochlear hair cells, Eps8 is not a main regulator of K+ channels expression in vestibular Type I hair cells.