ABSTRACT
Background Conotoxins have become a research hotspot in the neuropharmacology field for their high activity and specificity in targeting ion channels and neurotransmitter receptors. There have been reports of a conotoxin acting on two ion channels, but rare reports of a conotoxin acting on three ion channels. Methods Vr3a, a proline-rich M-superfamily conotoxin from a worm-hunting Conus varius, was obtained by solid-phase synthesis and identified by mass spectrometry. The effects of synthesized Vr3a on sodium, potassium and calcium currents were tested on rat DRG cells by patch clamp experiments. The further effects of Vr3a on human Cav1.2 and Cav2.2 currents were tested on HEK293 cells. Results About 10 μM Vr3a has no effects on the peak sodium currents, but can induce a ~10 mV shift in a polarizing direction in the current-voltage relationship. In addition, 10 μM Vr3a can increase 19.61 ± 5.12% of the peak potassium currents and do not induce a shift in the current-voltage relationship. An amount of 10 μM Vr3a can inhibit 31.26% ± 4.53% of the peak calcium currents and do not induce a shift in the current-voltage relationship. The IC50 value of Vr3a on calcium channel currents in rat DRG neurons is 19.28 ± 4.32 μM. Moreover, 10 μM Vr3a can inhibit 15.32% ± 5.41% of the human Cav1.2 currents and 12.86% ± 4.93% of the human Cav2.2 currents. Conclusions Vr3a can simultaneously affect sodium, potassium and calcium currents. This novel triple-target conotoxin Vr3a expands understanding of conotoxin functions.(AU)
Subject(s)
Proline/analysis , Conotoxins/analysis , Potassium , Sodium , CalciumABSTRACT
@#To elucidate possible mechanisms and targets of honokiol(Hnk)for hte treatment of pain, the effects of Hnk on tetrodoxin-senstive(TTX-S)sodium current(INa)were studied in acutely dissociated mouse dorsal root ganglion(DRG)neurons with whole-cell patch clamp technique. Hnk inhibited TTX-S INa currents in a concentration-dependent manner. At 30 μmol/L, Hnk obviously shifted the steady state activation of TTX-S INa toward more positive potentials by 10. 2 mV and prolonged the time course of recovery of sodium current, yet with no significant difference on recovery from inactivation of TTX-S sodium channel.
ABSTRACT
Objective To investigate the effect of carboxymethyl chitosan on sodium currents (I_(Na)) in single ventricular myocyte of rat,and to explore the mechanism of carboxymethyl chitosan at the ionic channel level.Methods Single ventricular myocyte of rat was isolated with enzymatic dissociation technique.Whole-cell patch clamp technique was used.The stimulating protocol was:holding potential—120 mV,command potential—80 mV to +20 mV,step potential 10 mV,duration 50 ms,stimulating interval 2 s.Results Carboxymethyl chitosan inhibited sodium channel in a dose-dependent manner.When holding potential was—120mV,carboxymethyl chitosan(0.1%,0.2%,0.3%) decreased the peak amplitude of I_(Na) density to 57.4%?6.7%,40.9%?5.4%and 16.1%?4.3%(P
ABSTRACT
AIM:To probe into the toxicological mechanism of sulfur dioxide (SO2) and its derivatives on cardiovascular system.METHODS: Effects of tea polyphenols (TP) on the increase in sodium current (INa) induced by SO2 derivatives in the cardiomyocytes were studied using the whole cell patch-clamp technique.RESULTS: ① The increase in INa induced by SO2 derivatives was inhibited by treating the cells with TP at different concentrations (10, 20 or 50 mg/L) in a dose dependent manner. At concentration of 50 mg/L, TP completely inhibited the increase in INa by SO2 derivatives. ② SO2 derivatives led to shift left of the activation curve. After application of TP at dose of 50 mg/L, the curve showed resumed significantly. ③ TP changed the inactivation process significantly. Before and after the application of SO2 derivatives, the half-inactivation voltage of INa was -(71.94?0.23) mV and -(65.79?0.69) mV (n=8, P0.05).CONCLUSION: TP inhibits the incremental effects of SO2 derivatives on INa, suggesting that the toxicity of SO2 on cardiomyocytes of rat is induced by free radical.