Distribution of the Na,K-ATPase α Subunit in the Rat Spiral Ganglion and Organ of Corti

Abstract

Processing of sound in the cochlea involves both afferent and efferent innervation. The Na,K-ATPase (NKA) is essential for cells that maintain hyperpolarized membrane potentials and sodium and potassium concentration gradients. Heterogeneity of NKA subunit expression is one mechanism that tailors physiology to particular cellular demands. Therefore, to provide insight into molecular differences that distinguish the various innervation pathways in the cochlea, we performed a variety of double labeling experiments with antibodies against three of the α isoforms of the NKA (NKAα1-3) and markers identifying particular subsets of neurons or supporting cells in whole mount preparations of the organ of Corti and spiral ganglion. We found that the NKAα3 is abundantly expressed within the membranes of the spiral ganglion somata, the type I afferent terminals contacting the inner hair cells, and the medial efferent terminals contacting the outer hair cells. We also found expression of the NKAα1 in the supporting cells that neighbor the inner hair cells and express the glutamate transporter GLAST. These findings suggest that both the NKAα1 and NKAα3 are poised to play an essential role in the regulation of the type I afferent synapses, the medial efferent synapses, and also glutamate transport from the afferent-inner hair cell synapse.

Sox2 Up-regulation and Glial Cell Proliferation Following Degeneration of Spiral Ganglion Neurons in the Adult Mouse Inner Ear

“…The selective survival advantage of type II over type I neurons has also been seen in other degeneration models, e.g., in ototoxic lesions (Spoendlin 1975;Lim 1976;Leake and Hradek 1988) transection of the cochlear nerve (Spoendlin 1975). A recent study revealed that differentiated expression patterns of Na,K-ATPase α isoforms are present in types I and II SGNs with Na,K-ATPase, α3 being present in type I SGNs but not in type II neurons (McLean et al 2009). Further studies on the molecular and functional characterization of these two types of neurons are needed to understand their differential response to insults.…”

Ouabain-Induced Cochlear Nerve Degeneration: Synaptic Loss and Plasticity in a Mouse Model of Auditory Neuropathy

“…Examination of confocal z-stacks immunostained for a Na/K ATPase expressed by ANF terminals in the IHC area (McLean et al, 2009) suggests that ouabain treatment elicits plasticity in synaptic architecture in addition to simple degeneration of synaptic elements. Most dramatic is the appearance of large nerve terminals (e.g., Fig.…”

“…The survival of type-IIs following kainate or acoustic overexposure may arise because these manipulations cause a type of glutamate excitotoxicity, and type-II neurons do not express the same complement of AMPA-type glutamate receptors as type-Is (Pujol et al, 1985;Liberman et al, 2011). The selective survival of the type-II neurons following ouabain may arise because ouabain-elicited neuronal death is due to blockade of the α3 subunit of the Na + /K + ATPase (Azarias et al, 2012), and this subunit is expressed by type-I, and not by type-II, spiral ganglion neurons (McLean et al, 2009). The selective survival of type-II neurons following cochlear nerve transection (Spoendlin and Suter, 1976) is not so easily explainable, and therefore suggests that the type-IIs may be generally more robust, perhaps because of a generally lower level of spike activity (Brown, 1994).…”

Subunit Isoform Selectivity in Assembly of Na,K-ATPase α-β Heterodimers

“…In contrast, other Na,K-ATPase subunit isoforms are expressed in a tissue-specific manner. The ␣ 2 isoform is expressed mainly in muscle and nervous system (1-3, 6, 7); the ␣ 3 isoform is expressed mainly in neurons (8,9), whereas the ␣ 4 isoform is found only in testis (10,11). The ␤ 2 isoform is expressed predominantly in brain and muscle (3,7), whereas the ␤ 3 isoform is mainly expressed in lung, testis, skeletal muscle, and liver (12,13).…”