蛋白丝/苏氨酸磷酸酶1和2A抑制药对大鼠三叉神经元电压依赖性钠通道的影响(英文)

目的通过研究蛋白丝/苏氨酸磷酸酶1和2A特异性抑制药冈田酸对大鼠三叉神经元电压依赖性钠电流的影响,探讨磷酸酶在细胞信号转导中的作用。方法在成年大鼠三叉神经元上进行全细胞膜片钳记录。结果1μmol·L-1冈田酸显著抑制总钠电流(INa-T) ,仅轻微抑制毒素不敏感型钠电流(INa-TTX-R) ,其抑制率分别为(20±13) %(n=9,P<0 .05)和(4±3) %(n=6, P<0 .05)。冈田酸对INa-T的激活曲线产生明显的超极化位移,半激活电压从给药前的-(13±8)mV升至给药后的-(16±7)mV(P<0 .05) ,但是对INa-TTX-R的激活曲线没有影响。结论①蛋白丝/苏氨酸磷酸酶参与了大鼠三叉神经元电压依赖性钠通道的调节。②大鼠三叉神经元存在多种电压依赖性钠通道,它们对冈田酸具有不同的敏感性。

Effects of inhibitor of serine/threonine protein phosphatases 1 and 2A on voltage-dependent sodium channels in rat trigeminal ganglion neurons

AIMTo investigate the role of serine/threonine protein phosphatases in regulation of cell signal transduction on voltage-dependent sodium channels in rat trigeminal ganglion (TRG) neurons. METHODSWhole-cell patch clamp techniques were used to record the total sodium current (INa-T) and the tetrodotoxin-resistant sodium current (INa-TTX-R) before and after okadaic acid, a potent inhibitor of the serine/threonine protein phosphatases 1 and 2A, perfusion on adult rat TRG neurons. RESULTS1μmol*L-1 okadaic acid inhibited INa-T by (20±13)% (n=9, P<0.05) and INa-TTX-R by (4±3)% (n=6, P<0.05), respectively. The inhibition on INa-T was significantly greater than that on INa-TTX-R (P<0.05). Furthermore, 1μmol*L-1 okadaic acid produced significant 3-4 mV hyperpolarizing shifts in the conductance-voltage curves of INa-T, while it had no effect on that of INa-TTX-R. CONCLUSIONThe serine/threonine protein phosphatases take part in the regulation of total and TTX-R sodium channels on rat TRG neurons. In addition, small-diameter TRG neurons express various voltage-gated sodium channel with different sensitivity to okadaic acid.