Analysis of KCNQ4 and KCNQ5 channel distribution and function in vestibular organ of knockout mice models

SPITZMAUL, GUILLERMO; CHABBERT CHRISTIAN; THOMAS J. JENTSCH

Amsterdam

Congreso; 7th FENS Forum of European Neuroscience.; 2010

THE FEDERATION OF EUROPEAN NEUROSCIENCE SOCIETIES (FENS)

The vestibular apparatus is the nonauditory portion of the inner ear. It plays roles in the spatialorientation, posture eye fixation during head movement. Vestibular organs are composed of 5sensory epithelia: the saccular and utricular macula and 3 cristas. Their sensory hair cells (HC), type I and type II, encode mechanosensory information that propagates from the apical mechanosensitive hair bundle to the basal calyx and bouton afferent synapses, respectively. It is still not clear how cells detect and transmit this information and of the molecules involved. In this regard, electrophysiological properties of these cells must be important. Both cells express outwardly rectifying K+ channels, but their properties are very different. Type I HC and their calyx afferents express both KCNQ4 and KCNQ5 and type II HC have been found to express KCNQ3 and KCNQ5. However KCNQ4 KO mice (Kcnq4-/-) do not exhibit overt vestibular phenotype such us a circling behavior. These could be due to compensation by KCNQ5. To analyze this possibility and study the contribution of different subunits to the M-current of vestibular hair cells we generated KCNQ4/5 double mutant mice (Kcnq4-/-Kcnq5dn/dn). First we determine the distribution of KCNQ4 and -5 in whole-mounts of vestibular organ of mice. We found KCNQ4 highly expressed in the central region of the cristae and the striola of utricle and less expressed in the peripheral regions. Surprisingly, KCNQ5 is only expressed in the peripheral regions of crista and utricle, where colocalizes with KCNQ4. Beta III tubulin-staining in slices indicates that the labeling is on type I HC or its calyx in both regions. In the striola, KCNQ4 also colocalizes with calretinin, a marker of calyxes of type I HC from the striola. We studied the potassium current of type I and type II HC from Kcnq4-/-, Kcnq5dn/dn and Kcnq4-/-Kcnq5dn/dn mice. No changes were observed on this current for all the mice models. Inconclusion, our data suggests that KCNQ4 and -5 are localized in the calyx afferent of type I HC and do not participate in the M-like current of these cells. We also found a differential distribution of KCNQ4 and KCNQ5 in vestibular organs, where KCNQ5 is only expressed in the extrastriolar region and KCNQ4 in whole the organ.