ABSTRACT
AIM@#To study the effects of crebanine on voltage-gated Na(+) channels in cardiac tissues.@*METHODS@#Single ventricular myocytes were enzymatically dissociated from adult guinea-pig heart. Voltage-dependent Na(+) current was recorded using the whole cell voltage-clamp technique.@*RESULTS@#Crebanine reversibly inhibited Na(+) current with an IC50 value of 0.283 mmol·L(-1) (95% confidence range: 0.248-0.318 mmol·L(-1)). Crebanine at 0.262 mmol·L(-1) caused a negative shift (about 12 mV) in the voltage-dependence of steady-state inactivation of Na(+) current, and retarded its recovery from inactivation, but did not affect its activation curve.@*CONCLUSION@#In addition to blocking other voltage-gated ion channels, crebanine blocked Na(+) channels in guinea-pig ventricular myocytes. Crebanine acted as an inactivation stabilizer of Na(+) channels in cardiac tissues.
Subject(s)
Animals , Female , Male , Aporphines , Pharmacology , Cells, Cultured , Down-Regulation , Drugs, Chinese Herbal , Pharmacology , Guinea Pigs , Heart Ventricles , Cell Biology , Metabolism , Myocytes, Cardiac , Metabolism , Stephania , Chemistry , Voltage-Gated Sodium Channel Blockers , Pharmacology , Voltage-Gated Sodium Channels , MetabolismABSTRACT
Rho kinase inhibition is beneficial for neurite outgrowth and nerve disorders, and the Rho kinase inhibitors have been regarded as promising agents to treat neural diseases. The main aim of the study was to elucidate how Rho kinase inhibitor Y-27632 regulates neurotransmitter norepinephrine synthesis and release in PC12 cells when neurite outgrowth was induced. PC12 cells were treated with Y-27632 for 6 days. The amount of norepinephrine synthesized in PC12 cells and the amount released evoked by acetylcholine or by KCl were determined by norepinephrine enzyme-linked immunosorbent assay kits. The results showed that the amount of norepinephrine both synthesized and released was down-regulated with a concentration-dependent relationship. Further results of Western blotting found that the protein expression of tyrosine hydroxylase and synapsin I (especially its active form, synapsin I phosphoSer603) was also down-regulated, which were directly related to synthesis and release of norepinephrine, respectively. All the results suggest that Y-27632 is able to down-regulate norepinephrine synthesis and release, the direct mechanism of which may be associated with down-regulation on expression of some proteins, including tyrosine hydroxylase and synapsin I.
