Effects of Kir2.1 gene transfection in cochlear hair cells and application of neurotrophic factors on survival and neurite growth of co-cultured cochlear spiral ganglion neurons.
Immature inner hair cells (IHCs) produce spontaneous action potentials, which may be associated with the survival of spiral ganglion neurons (SGNs) during early development. Later, this activity ceases in part by the expression of Kir channels. In the present study, SGNs were co-cultured with organ of Corti in which a Kir2.1 channel was over-expressed in an attempt to block the spontaneous activity of IHCs. The over-expression led to a reduced survival and neurite growth accompanied by increased SGN apoptosis. The enhanced activation of apoptosis was consistent with the inhibition of the survival-promoting pathway and the disruption of [Ca(2+)](i) homeostasis. Furthermore, the effect of Kir2.1 over-expression can be reversed by exogenous neurotrophic factors (NTFs). These results are consistent with the hypothesis that the earlier-than-normal expression of Kir2.1 in HCs inhibits their spontaneous activity required for SGN survival and neurite growth.
Ruan
Qingwei
Q
Otolaryngology Research Institute, Shanghai Jiaotong University, Shanghai 200233, PR China.
Chen
Dong
D
Wang
Zhengmin
Z
Chi
Fanglu
F
He
Jinchun
J
Wang
Jian
J
Yin
Shankai
S
D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006198:Hair Cells, Auditory / Q000166:cytology / Q000502:physiology; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009925:Organ of Corti / Q000166:cytology / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013136:Spiral Ganglion / Q000166:cytology*; D014162:Transfection; D051025:bcl-Associated Death Protein / Q000235:genetics / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; C489461:Kir2.1 channel; D009414:Nerve Growth Factors; D024661:Potassium Channels, Inwardly Rectifying; D011993:Recombinant Fusion Proteins; D051025:bcl-Associated Death Protein