Multiple pathways regulate the expression of genes encoding sodium channel subunits in developing neurons.
In primary cultures of fetal neurons, activation of sodium channels with either alpha-scorpion toxin or veratridine caused a rapid and persistent decrease of mRNAs encoding beta2 and different sodium channel alpha mRNAs. In contrast, beta1 subunit mRNA was up-regulated by sodium channel activation. This phenomenon was calcium-independent. The effects of activating toxins on mRNAs of different sodium channel subunits were mimicked by membrane depolarization. An important aspect of this study was the demonstration that cAMP also caused rapid reduction of alphaI, alphaII and alphaIII mRNA levels whereas beta1 subunit mRNA was up regulated and beta2 subunit mRNA was not affected. Sodium channel activation by veratridine was shown to increase cAMP immunoreactivity in cultured neurons, but alphaII mRNA down-regulation induced by activating toxins was not reversed by protein kinase A antagonists, indicating that this phenomenon is not protein kinase A dependent. The effects of cAMP and membrane depolarisation were antagonized by the PKA inhibitor H89. These results are indicative of the existence of multiple and independent regulatory pathways modulating the expression of sodium channel genes in the developing central nervous system.
Giraud
P
P
Laboratoire de Neurobiologie des Canaux Ioniques INSERM U464, IFR Jean Roche, Faculté de Médecine Nord, 13916 Marseille Cedex 20, France. giraud.p@jean-roche.univ-mrs.fr
Alcaraz
G
G
Jullien
F
F
Sampo
B
B
Jover
E
E
Couraud
F
F
Dargent
B
B
D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D005314:Embryonic and Fetal Development / Q000235:genetics; D005786:Gene Expression Regulation; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D015222:Sodium Channels / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*
D015222:Sodium Channels