Fig. 7.

Cytotoxic drugs differentially affect the electrophysiological properties of SH-SY5Y RA differentiated cells. a Top traces depict whole cell voltage clamp recordings of endogenous currents from representative naïve SH-SY5Y cells (Ctr, purple), retinoic acid differentiated (RA, black), and RA-differentiated cells treated with 5 nM HMB-isatin (red), 5 nM vinblastine (VBL, blue) and 5 nM vincristine (VCR, green). Currents were elicited by 25 ms step depolarizations to 0 mV from a Vh: -80 mV preceded by a 100 ms –120 mV pre-pulse (inset under Ctr). Scale bar: 1 nA. The insets below RA, HMB-isatin and VBL show voltage traces in response to current injection (50–100 pA, ∆10 pA, inset under VCR) that elicited action potentials from their respective Vh. Scale bars are: 10 mV and 100 ms. b and c Voltage dependent parameters of inward sodium currents in all groups obtained from IV stimulation protocols from −60 to 60 mV (∆10 mV, Vh: −80 mV). IVs from representative cells are shown in the inset on the right. b Slope and activation half voltage. c Right: maximal conductance (Gmax) and inward current density estimated from the ratio of peak current amplitude observed at 0 mV to the cell membrane capacitance (pA/pF). Ctr: non differentiated; RA: Retinoic acid differentiated; HMB-isatin: 5,7-dibromo-N-(p-hydroxymethylbenzyl)isatin treated RA cells; VBL: vinblastine treated RA cells; VCR: vincristine treated RA cells (drugs were applied overnight at 10 nM). Mean ± SEM from n = 5–24 cells per condition. Unpaired t-test compares RA against all other groups with a 95% confidence interval. Data are presented as means ± SEMs (n represents the number of individual recordings). A two-tailed, paired t-test was applied to compare current density between retinoic acid differentiated cells to the other experimental groups. Data presented is compiled from 3 independent experiments involving cell differentiation and drug treatment