Firing features and potassium channel content of murine spiral ganglion neurons vary with cochlear location

Abstract

Neurons from varied regions of the central nervous system can show widely divergent responses to electrical stimuli that are determined by cell-specific differences in ion channel composition. The well-ordered and highly characterized peripheral auditory system allows one to explore the significance of this diversity during the final stages of postnatal development. We examined the electrophysiological features of murine spiral ganglion neurons in vitro at a time when recordings could be made from the cell bodies before myelination. These cells carry information about sound stimuli from hair cell receptors in the basilar membrane and are arranged tonotopically. Spiral ganglion neuron responses to depolarizing current injection were assessed with whole-cell current clamp recordings from cells that were isolated separately from the apical and basal thirds of the mouse cochlea. These cells displayed systematic variation in their firing. Apex neurons (low frequency coding) showed longer latency, slowly adapting responses, whereas base neurons (high frequency coding) showed short latency, rapidly adapting responses to the same stimuli. This physiological diversity was mirrored by regional differences in ion channel content assessed immunohistochemically. Apex neurons had a preponderance of Kv4.2 subunits, whereas base neurons possessed greater levels of K(Ca), Kv1.1, and Kv3.1 subunits. Taken together, these results indicate that the distribution of a set of voltage-gated potassium channels may relate specifically to a particular range of coding frequencies. These studies also suggest that intrinsic properties of spiral ganglion neurons can contribute to the characteristic responses of the peripheral auditory system. Their potential role in development and adult function is discussed.

Functional Significance of K+ Channel β-Subunit KCNE3 in Auditory Neurons

“…Indeed, SGNs reacted positively to antibodies against Kv4.2 and KCNE3, and the two proteins were co-localized. In contrast, we did not detect positive staining with antibodies against Kv4.3, consistent with the results of previous studies (35,36).…”

“…To extend our study further, we rationalized that at least one of the Kv channels, under the regulation of KCNE3, would generate a transient current. Among the transient current channels in SGNs is Kv4.2 (35,36). We expressed mouse Kv4.2 in CHO cells, either singly or co-jointly with KCNE3.…”

Ion Channel Gene Expression in the Inner Ear

“…Our analysis suggests that the new isoform has a longer UTR than the canonical form, potentially with a previously unrecognized role in translational regulation. KCNB1, found in the mouse dataset was identified previously by PCR in X. laevis inner ear (Varela-Ramirez et al 1998), while KCNC1 was immunolocalized previously in mouse spiral ganglion (Adamson et al 2002) and developing chick cochlear ganglion and hair cells (Zhou et al 2001). Absent from cDNA libraries was Kv4.2 (KCND2), which is found in chick and mouse cochlear ganglion and hair cells (Adamson et al 2002;Rivolta et al 2002;Sokolowski et al 2004).…”

“…Studies of voltage-gated ion channel expression in inner ear tissues (Adamson et al 2002;Davis 2003) and expression of ionic currents during the development of hearing (Fuchs and Sokolowski 1990;Mammano and Ashmore 1996;Kros et al 1998;Michna et al 2003) provide evidence for the fundamental importance of ion channels in defining cellular specialization.…”

Temporal Considerations for Stimulating Spiral Ganglion Neurons with Cochlear Implants

“…To follow up on the Hodgkin-Huxley sodium channels, a modern survey of the type I SGN in mice revealed Nav1.6 channel subunits located at all nodes of Ranvier with particularly higher densities at the unmyelinated afferent process innervating the IHC layer and the nodes flanking the soma (Hossain et al 2005). In end-stage postnatal development murine type I SGN, Adamson et al (2002) found several potassium channel subunits. Specifically, the highfrequency basal neurons were dominated by highthreshold fast-delayed rectifier Kv3.1, low-threshold Kv1.1, and calcium-activated K + subunits, while the low-frequency apical neurons showed a majority of inactivating Kv4.2 subunits known for extending the latency of spiking near threshold.…”