Developmental alterations in the biophysical properties of Cav1.3 Ca2+ channels in mouse inner hair cells

摘要

Prior to hearing onset, spontaneous action potentials activate voltage-gated Cav1.3 Ca²⁺ channels in mouse inner hair cells (IHCs), which triggers exocytosis of glutamate and excitation of afferent neurons. In mature IHCs, Cav1.3 channels open in response to evoked receptor potentials, causing graded changes in exocytosis required for accurate sound transmission. Developmental alterations in Cav1.3 properties may support distinct roles of Cav1.3 in IHCs in immature and mature IHCs, and have been reported in various species. It is not known whether such changes in Cav1.3 properties occur in mouse IHCs, but this knowledge is necessary for understanding the roles of Cav1.3 in developing and mature IHCs. Here, we describe age-dependent differences in the biophysical properties of Cav1.3 channels in mouse IHCs. In mature IHCs, Cav1.3 channels activate more rapidly and exhibit greater Ca²⁺-dependent inactivation (CDI) than in immature IHCs. Consistent with the properties of Cav1.3 channels in heterologous expression systems, CDI in mature IHCs is not affected by increasing intracellular Ca²⁺ buffering strength. However, CDI in immature IHCs is significantly reduced by strong intracellular Ca²⁺ buffering, which both slows the onset of, and accelerates recovery from, inactivation. These results signify a developmental decline in the sensitivity of CDI to global elevations in Ca²⁺, which restricts negative feedback regulation of Cav1.3 channels to incoming Ca²⁺ ions in mature IHCs. Together with faster Cav1.3 activation kinetics, increased reliance of Cav1.3 CDI on local Ca²⁺ may sharpen presynaptic Ca²⁺ signals and improve temporal aspects of sound coding in mature IHCs.