科研之友
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摘要
The auxiliary subunit alpha(2)delta 2 modulates the abundance and function of voltage-gated calcium channels. Here we show that alpha(2)delta 2 mRNA is expressed in neonatal and mature hair cells. A functional alpha(2)delta 2-null mouse, the ducky mouse (du), showed elevated auditory brainstem response click and frequency-dependent hearing thresholds. Otoacoustic emissions were not impaired pointing to normal outer hair cell function. Peak Ca2+ and Ba2+ currents of mature du/du inner hair cells (IHCs) were reduced by 30-40%, respectively, and gating properties, such as the voltage of half-maximum activation and voltage sensitivity, were altered, indicating that Cav1.3 channels normally coassemble with alpha(2)delta 2 at IHC presynapses. The reduction of depolarization-evoked exocytosis in du/du IHCs reflected their reduced Ca2+ currents. Ca2+- and voltage-dependent K+ (BK) currents and the expression of the pore-forming BK alpha protein were normal. Ca(v)1.3 and Ca-v beta 2 protein expression was unchanged in du/du IHCs, forming clusters at presynaptic ribbons. However, the close apposition of presynaptic Ca(v)1.3 clusters with postsynaptic glutamate receptor GluA4 and PSD-95 clusters was significantly impaired in du/du mice. This implies that, in addition to controlling the expression and gating properties of Ca(v)1.3 channels, the largely extracellularly localized alpha(2)delta 2 subunit moreover plays a so far unknown role in mediating trans-synaptic alignment of presynaptic Ca2 + channels and postsynaptic AMPA receptors.
- 出版日期2016-10-26
