Johnson Stuart L, Marcotti Walter
Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK.
J Physiol. 2008 Feb 15;586(4):1029-42. doi: 10.1113/jphysiol.2007.145219. Epub 2008 Jan 3.
The Ca(2+) current (I(Ca)) in prehearing and adult inner hair cells (IHCs), the primary sensory receptors of the mammalian cochlea, is mainly carried by L-type (Ca(V)1.3) Ca(2+) channels. I(Ca) in immature and adult IHCs triggers the release of neurotransmitter onto auditory afferent fibres in response to spontaneous action potentials (APs) or graded receptor potentials, respectively. We have investigated whether the biophysical properties of I(Ca) vary between low- and high-frequency IHCs during cochlear development and whether its inactivation influences cellular responses. I(Ca) was recorded from gerbil IHCs maintained near physiological recording conditions. The size of I(Ca) in adult IHCs was about a third of that in immature cells with no apparent difference along the cochlea at both stages. The activation kinetics of I(Ca) were significantly faster in high-frequency IHCs, with that of adult cells being more rapid than immature cells. The degree of I(Ca) inactivation was similar along the immature cochlea but larger in high- than low-frequency adult IHCs. This inactivation was greatly reduced with barium but not affected by changing the intracellular buffer (BAPTA instead of EGTA). Immature basal IHCs showed faster recovery of I(Ca) from inactivation than apical cells allowing them to support a higher AP frequency. I(Ca) in adult IHCs was more resistant to progressive inactivation following repeated voltage stimulation than that of immature cells. This suggests that adult IHCs are likely to be suited for sustaining rapid and repeated release of synaptic vesicles, which is essential for sound encoding.
在听力发育前和成年的内毛细胞(IHCs)中,钙电流(I(Ca))是哺乳动物耳蜗的主要感觉感受器,主要由L型(Ca(V)1.3)钙通道传导。未成熟和成年内毛细胞中的I(Ca)分别响应自发动作电位(APs)或分级受体电位,触发神经递质释放到听觉传入纤维上。我们研究了在耳蜗发育过程中,低频和高频内毛细胞的I(Ca)生物物理特性是否存在差异,以及其失活是否会影响细胞反应。在接近生理记录条件下维持的沙鼠内毛细胞中记录I(Ca)。成年内毛细胞中I(Ca)的大小约为未成熟细胞的三分之一,在两个阶段沿耳蜗均无明显差异。高频内毛细胞中I(Ca)的激活动力学明显更快,成年细胞的激活动力学比未成熟细胞更快。未成熟耳蜗中I(Ca)的失活程度相似,但在成年高频内毛细胞中比低频内毛细胞更大。用钡可大大降低这种失活,但改变细胞内缓冲液(用BAPTA代替EGTA)则不影响失活。未成熟的基底内毛细胞比顶端细胞显示出更快的I(Ca)从失活状态恢复,使其能够支持更高的动作电位频率。成年内毛细胞中的I(Ca)在重复电压刺激后比未成熟细胞更能抵抗渐进性失活。这表明成年内毛细胞可能适合维持突触小泡的快速和重复释放,这对于声音编码至关重要。