Objective To investigate what effects BmKAS 1 (a polypeptide purified from the Chinese scorpion Buthus martensi Karsch [BmK] and named as BmK activator of skeletal muscle ryanodine receptor) and its upstream mi...Objective To investigate what effects BmKAS 1 (a polypeptide purified from the Chinese scorpion Buthus martensi Karsch [BmK] and named as BmK activator of skeletal muscle ryanodine receptor) and its upstream mixture BmK1 3 2 have on Na + channels in dorsal root ganglion (DRG) small diameter neurons Methods The whole cell patch clamp technique was used to investigate the effects of BmKAS 1 and BmK1 3 2 on Na + current in rat small diameter DRG neurons Results About 50% peak Na + current was suppressed by 10?μg/ml of BmK1 3 2 1 62?μg/ml of BmKAS 1 also blocked 50% peak Na + current, and there was an obvious dose dependent relationship Conclusion Both BmK1 3 2 and BmKAS 1 have a blocking effect on Na + channels, and this may one of the mechanisms for the analgetic effect of BmK1 3 2 and BmKAS 1展开更多
Objective In this study, the pharmacological kinetics of Buthus martensi Karsch （BmK） AS, a specific modulator of voltage-gated sodium channel site 4, was investigated on Nav1.3 expressed in Xenopus oocytes. Methods...Objective In this study, the pharmacological kinetics of Buthus martensi Karsch （BmK） AS, a specific modulator of voltage-gated sodium channel site 4, was investigated on Nav1.3 expressed in Xenopus oocytes. Methods Two-electrode voltage clamp was used to record the whole-cell sodium current. Results The peak currents of Nav1.3 were depressed by BmK AS over a wide range of concentrations （10, 100, and 500 nmol/L）. Most remarkably, BmK AS at 100 nmol/L hyperpolarized the voltage-dependence and increased the voltage-sensitivity of steady-state activation/inactivation. In addition, BmK AS was capable of hyperpolarizing not only the fast inactivation but also the slow inactivation, with a greater preference for the latter. Moreover, BmK AS accelerated the time constant and increased the ratio of recovery in Nav1.3 at all concentrations. Conclusion This study provides direct evidence that BmK AS facilitates steady-state activation and inhibits slow inactivation by stabilizing both the closed and open states of the Nav1.3 channel, which might result from an integrative binding to two receptor sites on the voltage-gated sodium channels. These results may shed light on therapeutics against Nav1.3-targeted pathology.展开更多
基金ThisprojectwassupportedbytheNationalNaturalScienceFoundationofChina (No 3 9870 70 2 ) theNationalDrugFoundationofChina(No
文摘Objective To investigate what effects BmKAS 1 (a polypeptide purified from the Chinese scorpion Buthus martensi Karsch [BmK] and named as BmK activator of skeletal muscle ryanodine receptor) and its upstream mixture BmK1 3 2 have on Na + channels in dorsal root ganglion (DRG) small diameter neurons Methods The whole cell patch clamp technique was used to investigate the effects of BmKAS 1 and BmK1 3 2 on Na + current in rat small diameter DRG neurons Results About 50% peak Na + current was suppressed by 10?μg/ml of BmK1 3 2 1 62?μg/ml of BmKAS 1 also blocked 50% peak Na + current, and there was an obvious dose dependent relationship Conclusion Both BmK1 3 2 and BmKAS 1 have a blocking effect on Na + channels, and this may one of the mechanisms for the analgetic effect of BmK1 3 2 and BmKAS 1
基金supported by grants from the National Basic Research Development Program of China (2010CB529806)the National Natural Science Foundation of China (31171064)+1 种基金the Key Research Program of Science and Technology Commissions of Shanghai Municipality (11JC1404300)the Leading Academic Discipline Project of Shanghai Municipal Education Commission (J50108)
文摘Objective In this study, the pharmacological kinetics of Buthus martensi Karsch （BmK） AS, a specific modulator of voltage-gated sodium channel site 4, was investigated on Nav1.3 expressed in Xenopus oocytes. Methods Two-electrode voltage clamp was used to record the whole-cell sodium current. Results The peak currents of Nav1.3 were depressed by BmK AS over a wide range of concentrations （10, 100, and 500 nmol/L）. Most remarkably, BmK AS at 100 nmol/L hyperpolarized the voltage-dependence and increased the voltage-sensitivity of steady-state activation/inactivation. In addition, BmK AS was capable of hyperpolarizing not only the fast inactivation but also the slow inactivation, with a greater preference for the latter. Moreover, BmK AS accelerated the time constant and increased the ratio of recovery in Nav1.3 at all concentrations. Conclusion This study provides direct evidence that BmK AS facilitates steady-state activation and inhibits slow inactivation by stabilizing both the closed and open states of the Nav1.3 channel, which might result from an integrative binding to two receptor sites on the voltage-gated sodium channels. These results may shed light on therapeutics against Nav1.3-targeted pathology.
