Activation of P-type calcium channel regulates a unique thapsigargin-sensitive calcium pool in embryonic motoneurons

By regulating voltage-dependent Ca2+ influx and intracellular Ca2+ homeostasis, electrical activity plays a central role in motoneuron development. Dissociated cultures of purified embryonic rat motoneurons were used to explore the molecular mechanisms by which Ca2+ influx control [Ca2+], transients in these neurons. Thapsigargin (250 nM) and cyclopiazonic acid (10 muM), which deplete Ca2+ stores in the endoplasmic reticulum, decrease by 30% the depolarization-induced [Ca2+](i) transients in motoneurons without affecting voltage-activated calcium currents. This thapsigargin-sensitive intracellular Ca2+ pool differs from other previous described Ca2+ stores that are sensitive to ryanodine or caffeine, inositol triphosphate, insulin and from mitochondrial Ca2+ pools. Thapsigargin affected the Ca(v)2.1 P-type Ca2+ channel component of the de polarization-induced [Ca2+](i) transient in motoneurons but spared [Ca2+](i) transient induced by Ca(v)1 L-type and Ca(v)2.2 N-type Ca2+ channel components, suggesting a close functional relationship between Ca(v)2.1 subunit and this unique thapsigargin-sensitive Ca2+ store. Altogether the present results demonstrate a new pathway, used by embryonic motoneurons, to regulate Ca2+ signalling through voltage-activated (Ca(v)2.1) Ca2+ channels.