Neuronal Na+ channels are functionally inhibited in the adult in response to acute O2 deprivation. Since prolonged
hypoxia may not only affect channel function, but also its expression, we hypothesized that long-term
hypoxia alters Na+ channel density. This alteration may depend on age, because we have found major differences in neuronal responses to
hypoxia between the immature and adult. In the present work, we used northern blots, slot blots,
saxitoxin binding and autoradiography to ask whether: (i) prolonged
hypoxia alters Na+ channel
messenger RNA and
protein levels in the brain; (ii) there is a difference between the adult and prenatal brains regarding Na+ channel expression with hypoxic exposure; and (iii) regional differences in Na+ channel expression occur in
hypoxia-exposed brains. Our results show the following. (1) Na+ channel
messenger RNA and
saxitoxin binding density decreased after prolonged
hypoxia in adult brain homogenates; this is in sharp contrast to the changes observed in fetal brains, which tended to increase Na+ channel
messenger RNA and
protein after
hypoxia. (2) Changes in
saxitoxin binding density are related to alterations in the number of
saxitoxin binding sites and not to binding affinity, since there was no major change in Kd values between the
hypoxia and naive groups. (3) The
hypoxia-induced Na+ channel expression was heterogeneous, with major differences between rostral regions (e.g., the cortex) and caudal regions (e.g., the medulla and pons). We speculate that down-regulation of Na+ channels during long-term
hypoxia in mature brains is an adaptive cellular response, aimed at minimizing the mismatch between energy supply and demand, since maintenance of Na+ gradients is a major energy-requiring process. However, the prenatal brain does not depend on this adaptive mechanism in response to hypoxic stress.