Specific properties of sodium currents in multipotent striatal progenitor cells

This study investigates the impact of intrinsic currents on early neural development. A rat striatal ST14A cell line immortalized by SV40 large T antigen was employed as a model system because these cells act as multipotent neural progenitors when maintained at a permissive temperature of 33 degrees C. The whole-cell patch-clamp, molecular and immunocytochemical experiments point to a unique role of sodium currents in the multipotential stage of neural development. In initial experiments, action potential-like responses were only present when multipotential ST14A cells were substantially hyperpolarized. This led us to presume that sodium channels were only recruited during deep hyperpolarization. Subsequent voltage-clamp studies confirmed a remarkably hyperpolarized steady-state inactivation of the sodium currents and also showed that the underlying channels were tetrodotoxin resistant. Direct comparison with cells whose neuronal fate was already determined, i.e. short-term cultured striatal cells isolated at embryonic day 14 and after birth (post-natal day 0), showed that both traits are unique to ST14A cells. However, sodium currents in all three groups had a fast time- and voltage-dependent activation, as well as full inactivation with roughly similar kinetics. The peculiarity in ST14A might be explained by a relative excess of heart-type Na(V)1.5 and particularly its splice variant Na(V)1.5a, as suggested by reverse transcription-polymerase chain reaction results. We conclude that multipotent neural progenitor cells express Na(+) channels in their membrane irrespective of their fate but these channels have little effect due to their subunit composition, which is regulated by alternative splicing.