CaBP1 regulates Ca1 L-type Ca channels and their coupling to neurite growth and gene transcription in mouse spiral ganglion neurons.

CaBP1 is a Ca binding protein that is widely expressed in neurons in the brain, retina, and cochlea. In heterologous expression systems, CaBP1 interacts with and regulates voltage-gated Ca Ca channels but whether this is the case in neurons is unknown. Here, we investigated the cellular functions of CaBP1 in cochlear spiral ganglion neurons (SGNs), which express high levels of CaBP1. Consistent with the role of CaBP1 as a suppressor of Ca-dependent inactivation (CDI) of Ca1 (L-type) channels, Ca1 currents underwent greater CDI in SGNs from mice lacking CaBP1 (C-KO) than in wild-type (WT) SGNs. The coupling of Ca1 channels to downstream signaling pathways was also disrupted in C-KO SGNs. Activity-dependent repression of neurite growth was significantly blunted and unresponsive to Ca1 antagonists in C-KO SGNs in contrast to WT SGNs. Moreover, Ca1-mediated Ca signals and phosphorylation of cAMP-response element binding protein were reduced in C-KO SGNs compared to WT SGNs. Our findings establish a role for CaBP1 as an essential regulator of Ca1 channels in SGNs and their coupling to downstream pathways controlling activity-dependent transcription and neurite growth.