Naked mole-rat cortical neurons are resistant to acid-induced cell death.
Mol Brain. 2018-05-09; 11(1):
DOI: 10.1186/s13041-018-0369-4
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1. Mol Brain. 2018 May 9;11(1):26. doi: 10.1186/s13041-018-0369-4.
Naked mole-rat cortical neurons are resistant to acid-induced cell death.
Husson Z(1), Smith ESJ(2).
Author information:
(1)Department of Pharmacology, University of Cambridge, Tennis Court Road,
Cambridge, CB2 1PD, UK.
(2)Department of Pharmacology, University of Cambridge, Tennis Court Road,
Cambridge, CB2 1PD, UK. .
Regulation of brain pH is a critical homeostatic process and changes in brain pH
modulate various ion channels and receptors and thus neuronal excitability.
Tissue acidosis, resulting from hypoxia or hypercapnia, can activate various
proteins and ion channels, among which acid-sensing ion channels (ASICs) a family
of primarily Na+ permeable ion channels, which alongside classical excitotoxicity
causes neuronal death. Naked mole-rats (NMRs, Heterocephalus glaber) are
long-lived, fossorial, eusocial rodents that display remarkable
behavioral/cellular hypoxia and hypercapnia resistance. In the central nervous
system, ASIC subunit expression is similar between mouse and NMR with the
exception of much lower expression of ASIC4 throughout the NMR brain. However,
ASIC function and neuronal sensitivity to sustained acidosis has not been
examined in the NMR brain. Here, we show with whole-cell patch-clamp
electrophysiology of cultured NMR and mouse cortical and hippocampal neurons that
NMR neurons have smaller voltage-gated Na+ channel currents and more
hyperpolarized resting membrane potentials. We further demonstrate that
acid-mediated currents in NMR neurons are of smaller magnitude than in mouse, and
that all currents in both species are reversibly blocked by the ASIC antagonist
benzamil. We further demonstrate that NMR neurons show greater resistance to
acid-induced cell death than mouse neurons. In summary, NMR neurons show
significant cellular resistance to acidotoxicity compared to mouse neurons,
contributing factors likely to be smaller ASIC-mediated currents and reduced NaV
activity.
DOI: 10.1186/s13041-018-0369-4
PMCID: PMC5941639
PMID: 29739425 [Indexed for MEDLINE]