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

Min Liang; Hanwei Liu; Xinlu Yin; Lina Gong; Huiqun Jie; Luyang Wang; Haibo Shi; Jingchun He; Penghui Chen; Jingrong Lu; Shankai Yin; Jun Yang

doi:10.1016/j.neulet.2022.136747

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

Neurosci Lett. 2022 Jul 27:784:136747. doi: 10.1016/j.neulet.2022.136747. Epub 2022 Jun 18.

Authors

Min Liang¹, Hanwei Liu², Xinlu Yin³, Lina Gong², Huiqun Jie¹, Luyang Wang⁴, Haibo Shi², Jingchun He¹, Penghui Chen¹, Jingrong Lu⁵, Shankai Yin⁶, Jun Yang⁷

Affiliations

¹ Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
² Department of Otorhinolaryngology, the Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
³ Department of Otorhinolaryngology-Head and Neck Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
⁴ Program in Neurosciences & Mental Health, SickKids Research Institute, Department of Physiology, University of Toronto, Toronto, ON, Canada.
⁵ Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address: [email protected].
⁶ Department of Otorhinolaryngology, the Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China. Electronic address: [email protected].
⁷ Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address: [email protected].

PMID: 35724761
DOI: 10.1016/j.neulet.2022.136747

Abstract

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.

Keywords: Bilirubin encephalopathy; Ca(2+) overload; Nicotinamide adenine dinucleotide; Ventral cochlear nucleus; Voltage-gated calcium channels; Whole-cell patch-clamp recording.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bilirubin / pharmacology
Calcium
Cochlear Nucleus*
NAD / pharmacology
Neurons

Substances

NAD
Bilirubin
Calcium