Role of voltage-gated Na+ channels in hypoxia-induced neuronal injuries

1. Mammalian neurons in the central nervous system are vulnerable to oxygen deprivation. In clinical conditions, such as stroke or apnoea, permanent l oss of neuronal functions can occur within minutes of severe hypoxia. 2. Recent studies have focused on the role of Na+ in acute neuronal respons es to hypoxia. These studies have shown that the influx of extracellular Na + is an important factor in hypoxia-induced injury and that blockade of vol tage-gated Na+ channels reduces hypoxic responses and injury of neurons. Ye t, the mechanism underlying the effect of blockade of Na+ channels on hypox ic injury is unclear. 3. The aim of the present review is to discuss the above topics given the c urrent understanding of the role of Na+ channels in hypoxia and its implica tions on therapeutic strategy for preventing hypoxia-induced neurological d amage. 4. It has been known that the maintenance of ionic homeostasis and membrane properties in neurons are improved by reducing the activity of voltaged-ga ted Na+ channels during acute hypoxia. 5. Recent studies suggest that persistent Na+ current and Na+-dependent exc hangers may play a role in Na+ influx and neuronal injury during hypoxia. 6. The neuroprotective action of blockers of the Na+ channel may also be vi a the improved maintainence of intracellular energy levels because the acti on is dependent on cellular energy levels and extracellular glucose during hypoxia. 7. Hence, the blockade of voltage-gated Na+ channels reduces the excitabili ty of neurons, Na+ influx and the accumulation of intracellular Na+. These improve the ionic homeostasis and cellular energy levels and, thus, prevent hypoxia-induced neuronal injury and neuronal damage mediated by Ca2+ overl oad.