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.
Wasner
Ulrike
U
Department of Neurology, University of Rostock, Rostock, Germany.
Geist
Beate
B
Battefeld
Arne
A
Bauer
Peter
P
Müller
Jana
J
Rolfs
Arndt
A
Strauss
Ulf
U
D017398:Alternative Splicing; D000818:Animals; D002460:Cell Line; D015640:Ion Channel Gating / Q000502:physiology; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism; D013779:Tetrodotoxin / Q000378:metabolism
D020033:Protein Isoforms; D021122:Protein Subunits; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013779:Tetrodotoxin; D012964:Sodium