Altered sodium currents in auditory neurons of congenitally deaf mice.
Sodium currents are essential for action potential generation and propagation in most excitable cells. Appropriate tuning of these currents can be modulated both developmentally and in response to activity. Here we use a mouse model of congenital deafness (dn/dn- asymptomatic deafness associated with hair cell degeneration) to investigate the effect of lack of activity in the expression of Na(+) currents in neurons from the medial nucleus of the trapezoid body (MNTB). Patch-clamp recordings show that at postnatal day (P) 14, both normal and deaf mice display a significant amount of persistent and resurgent Na(+) currents. However, the persistent current is greater in deaf mice than in normal mice, and resurgent current kinetics are slower in deaf mice. At P7, resurgent currents are not present in either group. MNTB immunohistochemistry demonstrates that Nav1.1 subunits are expressed postsynaptically in both P14 normal and deaf mice, while postsynaptic Nav1.6 staining was only observed in deaf mice. Labelling of Nav1.6 subunits in different age groups revealed that at younger ages (P7), both normal and deaf mice express this protein. Nav1.6 staining was not observed in MNTB neurons of P28 normal mice, whereas it is maintained in deaf mice cells until much later (P28). At P7, none of the groups displayed resurgent currents (despite the detection of Nav1.6 subunits at this age group); this suggests that factors other than alpha subunits are important for modulating these currents in MNTB cells. Our results emphasize the importance of activity during development in regulating Na(+) channels.
Leão
Richardson N
RN
Synapse and Hearing Laboratory, Division of Neuroscience, John Curtin School of Medical Research, Australian National University, PO Box 334, Canberra, ACT 0200, Australia. Richardson.Leao@anu.edu.au
Naves
Marcell M
MM
Leão
Katarina E
KE
Walmsley
Bruce
B
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001306:Auditory Pathways / Q000033:anatomy & histology / Q000502:physiology; D003638:Deafness / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D021122:Protein Subunits / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism*
D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; C491046:Scn8a protein, mouse; D015222:Sodium Channels; D012964:Sodium