Calcium- and calmodulin-dependent inactivation of calcium channels in inner hair cells of the rat cochlea
Calcium- and calmodulin-dependent inactivation of calcium channels in inner hair cells of the rat cochlea
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DOI：
10.1152/jn.01174.2007
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发表时间：
2008-05-01
影响因子：
2.5
通讯作者：
Fuchs, Paul
中科院分区：
文献类型：
--
作者：
Grant, Lisa;Fuchs, Paul
在离体制备大鼠耳蜗顶转器官的过程中，研究了内毛细胞中电压门控钙通道的调节。在钾通道阻滞剂存在下，全细胞电压钳显示出向内的钙电流，具有毫秒激活和失活动力学。当温度从22℃升高到37℃时，未成熟ihc[出生后< 12天（P12）]的钙电流幅度增加了三倍，并出现更明显的失活。这被确定为钙依赖性失活（CDI），基于其对外部钙（钡替代）的依赖，对内部钙缓冲的敏感性，以及电压依赖性（反映钙的驱动力）。在P12开始听力后，IHC钙电流幅度和失活程度大大降低。尽管CDI比听前IHC小，但在成熟IHC中，CDI在静息膜电位附近仍然显著。应用内质钙泵阻滞剂苯并对苯二酚可增强成熟ihc的CDI。相反，未成熟ihc中的CDI被钙调素抑制剂降低。因此，哺乳动物IHCs中的电压门控钙通道受钙调素介导的CDI过程的影响。CDI的程度取决于钙缓冲机制的平衡，并可能受到钙调素特异性过程的调节。CDI提供了一种方法，可以根据毛细胞静息电位和稳态钙流入的变化来调节自发递质释放的速率。
Modulation of voltage-gated calcium channels was studied in inner hair cells (IHCs) in an ex vivo preparation of the apical turn of the rat organ of Corti. Whole cell voltage clamp in the presence of potassium channel blockers showed inward calcium currents with millisecond activation and deactivation kinetics. When temperature was raised from 22 to 37 C, the calcium currents of immature IHCs [< 12 days postnatal (P12)] increased threefold in amplitude, and developed more pronounced inactivation. This was determined to be calcium-dependent inactivation (CDI) on the basis of its reliance on external calcium (substitution with barium), sensitivity to internal calcium-buffering, and voltage dependence (reflecting the calcium driving force). After the onset of hearing at P12, IHC calcium current amplitude and the extent of inactivation were greatly reduced. Although smaller than in prehearing IHCs, CDI remained significant in the mature IHC near the resting membrane potential. CDI in mature IHCs was enhanced by application of the endoplasmic calcium pump blocker, benzo-hydroquinone. Conversely, CDI in immature IHCs was reduced by calmodulin inhibitors. Thus voltage-gated calcium channels in mammalian IHCs are subject to a calmodulin-mediated process of CDI. The extent of CDI depends on the balance of calcium buffering mechanisms and may be regulated by calmodulin-specific processes. CDI provides a means for the rate of spontaneous transmitter release to be adjusted to variations in hair cell resting potential and steady state calcium influx.