Up‐Regulation of Sodium Channel Subunit mRNAs and Their Cell Surface Expression by Antiepileptic Valproic Acid: Activation of Calcium Channel and Catecholamine Secretion in Adrenal Chromaffin Cells

Abstract

Treatment of cultured bovine adrenal chromaffin cells with a therapeutic concentration (0.6 mM) of valproic acid (VPA) for >24 h caused a time-dependent (t 112 = 74 h) increase in [ 3H]saxitoxinbinding up to 1.4fold without altering the KD value; it was prevented by the simultaneous treatment with cycloheximide (an inhibitor of protein synthesis). VPA also raised Na~channel aand /3 1-subunit mRNA levels 1.4-and 1.7-fold at 24 h, and 1 .6-and 1.8-fold at 72 h, respectively. Chronic (but not acute) exposure to VPA enhanced

Pooling samples within microarray studies: a comparative analysis of rat liver transcription response to prototypical toxicants

“…Each of the three transcripts had a high level of hybridization to the Affymetrix mismatch probes, providing an explanation for why MAS5 did not pick up the change. Interestingly, VPA has been shown to modulate sodium channel-␤1, and this is likely associated with its pharmacological mechanism of action (51). The increase in lanosterol-14-demethylase transcript after VPA treatment has not been reported previously.…”

Valproic Acid Antagonizes the Capacity of Other Histone Deacetylase Inhibitors To Activate the Epstein-Barr Virus Lytic Cycle

“…VPA increases GABA levels and augments signaling through this pathway by altering GABA metabolic pathways and influencing GABA receptor activity (25,67,69). VPA impinges on several other molecular and cellular processes, such as the activity and expression of ionic channels, Wnt signaling, and Akt regulation (6,17,19,27,67,92,99). Activation of the extracellular signal-regulated kinase (ERK) pathway is commonly observed following VPA treatment (67,104).…”

Destabilization of Nav1.7 Sodium Channel α-Subunit mRNA by Constitutive Phosphorylation of Extracellular Signal-Regulated Kinase: Negative Regulation of Steady-State Level of Cell Surface Functional Sodium Channels in Adrenal Chromaffin Cells

“…22 Na ϩ influx was measured by incubating the cells with 2 Ci 22 NaCl at 37°C for 5 min in 1 ml of KRP buffer in the absence or presence of veratridine, ouabain, PbTx-3, and nicotine. The cells were washed with ice-cold KRP buffer, solubilized in 10% Triton X-100, and counted for radioactivity (Wada et al, 1986(Wada et al, , 1992Yamamoto et al, 1996Yamamoto et al, , 1997Yanagita et al, 1996;Yuhi et al, 1996;Shiraishi et al, 2001a,b).…”

“…In adrenal chromaffin cells, our previous studies showed that nicotinic receptor agonists rapidly increase 22 Na ϩ influx within 1 min, which passes through nicotinic receptor-associated cation channels (but not through voltage-dependent Na ϩ channels) and gates voltage-dependent Ca 2ϩ channels (Wada et al, 1986;Yamamoto et al, 1997). In the present study, we examined whether treatment of adrenal chromaffin cells with serum deprivation, 50 M PD98059 or 10 M U0126 for 24 h could alter the activity of nicotinic receptorassociated cation channels.…”