Neural activity is crucial for cell survival and fine patterning of neuronal connectivity during neurodevelopment. To investigate the role in vivo of sodium channels (NaCh) in these processes, we generated knockout mice deficient in brain NaChα(II). NaChα(II)/(-/-) mice were morphologically and organogenically indistinguishable from their NaChα(+/-) littermates. Notwithstanding, NaChα(II)(-/-) mice died perinatally with severe hypoxia and massive neuronal apoptosis, notably in the brainstem. Sodium channel currents recorded from cultured neurons of NaChα(II)(-/-) mice were sharply attenuated. Death appears to arise from severe hypoxia consequent to the brainstem deficiency of NaChα(II). NaChα(II) expression is, therefore, redundant for embryonic development but essential for postnatal survival.
Planells-Cases, R., Caprini, M., Zhang, J., Rockenstein, E.M., Rivera, R.R., Murre, C., et al. (2000). Neuronal death and perinatal lethality in voltage-gated sodium channel α(II)-deficient mice. BIOPHYSICAL JOURNAL, 78(6), 2878-2891 [10.1016/S0006-3495(00)76829-9].
Neuronal death and perinatal lethality in voltage-gated sodium channel α(II)-deficient mice
Caprini M.;
2000
Abstract
Neural activity is crucial for cell survival and fine patterning of neuronal connectivity during neurodevelopment. To investigate the role in vivo of sodium channels (NaCh) in these processes, we generated knockout mice deficient in brain NaChα(II). NaChα(II)/(-/-) mice were morphologically and organogenically indistinguishable from their NaChα(+/-) littermates. Notwithstanding, NaChα(II)(-/-) mice died perinatally with severe hypoxia and massive neuronal apoptosis, notably in the brainstem. Sodium channel currents recorded from cultured neurons of NaChα(II)(-/-) mice were sharply attenuated. Death appears to arise from severe hypoxia consequent to the brainstem deficiency of NaChα(II). NaChα(II) expression is, therefore, redundant for embryonic development but essential for postnatal survival.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
