Embryonic stem-cell derived neurones express a maturation dependent pattern of voltage-gated calcium channels and calcium-binding proteins

There are remarkable changes of calcium binding proteins and voltage depend ent Ca2+ channel subtypes during in vitro differentiation of embryonic stem cell derived neurons. To observe these maturation dependent changes neuron es were studied using combined immunohistochemical, patch clamp and videomi croscopic time lapse techniques. Embryonic stem cell derived neuronal matur ation proceeds from apolar to bi- and multipolar neurones, expressing all C a2+ channel subtypes. There is, however, a clear shift in channel contribut ion to whole cell current from apolar neurones with mainly N- and L-type ch annel contribution in favour of P/Q- and R-type participation in bi- and mu ltipolar cells. Expression of the calcium binding protein parvalbumin could be detected in bipolar. while calretinin and calbindin was preferentially found in multipolar neurones. Our data provides new insights into fundament al neurodevelopmental mechanisms related to Ca2+ homeostasis, and clarifies contradictory reports on the development of Ca2+ channel expression using primary cultures of neurones already committed to certain brain compartment s. (C) 2000 ISDN. Published by Elsevier Science Ltd. All rights reserved.