NAD+ attenuates bilirubin-induced augmentation of voltage-gated calcium currents in neurons of the ventral cochlear nucleus.

• Bilirubin concentration-dependently promoted Ca2+ influx into brainstem auditory neurons from neonatal rats. • Low concentration of NAD+ mitigated excess Ca2+ influx induced by bilirubin. • NAD+ prevented bilirubin-induced enhancement of voltage-gated calcium currents. Nicotinamide adenine dinucleotide (NAD+) is a ubiquitous molecule with wide-ranging roles in several cell processes, such as regulation of calcium homeostasis and protection against cell injuries. However, the roles of NAD+ in neuroprotection is poorly understood. The main neurons in ventral cochlear nucleus (VCN) are highly susceptible to bilirubin-associated excitotoxicity. We investigated the effects of NAD+ on VCN neurons by whole cell patch-clamp recordings. We found that NAD+ effectively reverses and inhibits bilirubin-mediated enhancement of voltage-gated calcium (VGCC) currents in VCN neurons. Moreover, NAD+ itself did not affect VGCC currents. These results collectively suggest that NAD+ may be neuroprotective by attenuating Ca2+ influx to suppress bilirubin-induced intracellular Ca2+ overloads. Our research provides a basis for evaluation of NAD+ as a promising therapeutic target for bilirubin encephalopathy and excitotoxicity associated with other neurological disorders. [ABSTRACT FROM AUTHOR]