Enhancement of Veratridine-Induced Sodium Dynamics in NG108-15 Cells during Differentiation

Abstract

Developmental changes in dynamics of Na⁺ were studied in neuroblastoma×glioma hybrid NG108-15 cells during differentiation which was induced by dibutyryl cAMP (Bt₂cAMP). Ratiometric Na⁺ imaging with a Na⁺-sensitive fluorescent dye SBFI (sodium-binding benzofuran isophthalate) revealed that the intracellular Na⁺ concentration ([Na⁺]_i) was not affected by the application of high K⁺ (60 mM) solution to either control or differentiated cells. When cells were exposed to 50 μM veratridine (Vtd), an agonist of voltage-sensitive sodium channels (VSSCs), a significant increase in [Na⁺]_i was observed in differentiated but not in undifferentiated cells. Calculated mean [Na⁺]_i value increased from the basal 10.4 to 44.1 mM in response to 50 μM Vtd. This Vtd response was reversibly inhibited by tetrodotoxin (TTX), a specific blocker for VSSCs, in a dose-dependent manner (IC₅₀=1 nM). It is suggested that VSSCs in NG108-15 cells are sensitive to TTX and Vtd and that the number of VSSCs increases during differentiation.