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Specific properties of sodium currents in multipotent striatal progenitor cells


Dr U. Strauss, 2Institute for Cell Biology and Neurobiology, as above.


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°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 NaV1.5 and particularly its splice variant NaV1.5a, 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.