Similarity and mutual exclusion of NMDA- and proton-activated transient Na+-currents in rat tectal neurons

Vertebrate neurons respond to rapid elevation of [H+]o with transient Na+-selective currents (INa(H]. Since INa(H) and voltage-activated Ca2+-currents (ICa(V] are mutually exclusive and similarly affected by inorganic and organic Ca2+-blockers, it has been suggested that such a Na+-permeable state evolves from protonation of Ca2+-channels. We show here that in cultured neurons from embryonic rat superior colliculus N-methyl-D-aspartate (NMDA) provides conditions for generation of a current identical with INa(H), but without the requirement of an increase in free [H+]o. The transient NMDA-activated current (I(NMDA)T) is occluded by INa(H). Its time course is similar to that of INa(H). Both currents are inactivated by long exposure to high [H+]o. I(NMDA)T displays a linear current-voltage (I-V) relationship under conditions which cause a negative slope in the I-V relationship of the persistent NMDA-activated current (I(NMDA)P). This suggests that the biphasic response of tectal neurons to the glutamate-agonist NMDA results from superposition of two different currents.