Expression of depolarizing voltage- and transmitter-activated currents in neuronal precursor cells from the rat brain is preceded by a proton-activated sodium current.

The early expression of amiloride-sensitive proton-activated sodium currents (INa(H] was demonstrated using the giga-seal whole-cell voltage clamp technique in cells from the primordial tectum of E12 rat embryos. Less than 10% of these cells stained for tetanus toxin receptors after 2 h in vitro. However, after 10 h in vitro all cells with neuronal geometry were tetanus toxin-positive and capable of generating voltage-activated Na currents (INa(V] and high-voltage activated Ca2+-currents (ICa(HV]. INa(H) was expressed roughly in parallel with INa(V) and ICa(HV), but exceeded the former currents in amplitude by 50-100 times, reaching 600 pA and more. In 25% of the cells tested within the first 5 h in vitro INa(H) was, in fact, the only cationic inward current resolved. Responses to quisqualate and kainate appeared only after 3 days in vitro, and responses to N-methyl-D-aspartate/glycine were seen only after 4 days in vitro. These results suggest that the channels carrying INa(H) are present at the earliest stages of neuronal development.