Neuronal death and perinatal lethality in voltage-gated sodium channel alpha(II)-deficient mice

Neural activity is crucial for cell survival and fine patterning of neurona l connectivity during neurodevelopment, To investigate the role in vivo of sodium channels (NaCh) in these processes, we generated knockout mice defic ient in brain NaCh alpha(II). NaCh alpha(II)(-/-) mice were morphologically and organogenically indistinguishable from their NaCh alpha(+/-) littermat es. Notwithstanding, NaCh alpha(II)(-/-) mice died perinatally with severe hypoxia and massive neuronal apoptosis, notably in the brainstem. Sodium ch annel currents recorded from cultured neurons of NaCh alpha(II)(-/-) mice w ere sharply attenuated. Death appears to arise from severe hypoxia conseque nt to the brainstem deficiency of NaCh alpha(II). NaCh alpha(II) expression is, therefore, redundant for embryonic development but essential for postn atal survival.