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+]i transients in these neurons. Thapsigargin (250 nm) and cyclopiazonic acid (10 micro m), 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 Cav2.1 P-type Ca2+ channel component of the depolarization-induced [Ca2+]i transient in motoneurons but spared [Ca2+]i transient induced by Cav1 L-type and Cav2.2 N-type Ca2+ channel components, suggesting a close functional relationship between Cav2.1 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 (Cav2.1) Ca2+ channels.
Inserm U-583, Université Montpellier II, Place Eugène Bataillon, Case 089, 34095, Montpellier, Cedex 5, France.
Frédérique
F
Scamps
Anne
A
Roig
Hassan
H
Boukhaddaoui
Sylvain
S
André
Sylvie
S
Puech
Jean
J
Valmier
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020865:Calcium Channels, P-Type / Q000378:metabolism*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005260:Female; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D019284:Thapsigargin / Q000494:pharmacology*
D020865:Calcium Channels, P-Type; D019284:Thapsigargin; D002118:Calcium