Modulation of neuron Nav1.2 channel by sigma-1 receptor agonist

• 作 者: Xiao-Fei GAO Chang-Long HU Yan-AiMEI
• 机 构: Institutes of Brain Science, School of Life Sciences and State Key Laboratory of Medical Neurobiolog
• 出 处: 中国神经科学学会第九届全国学术会议暨第五届会员代表大会
• 发表日期: 2011年1期
• 关键词: rNav1.2 channel σ-1 receptor agonist (+)-SKF 10047 PKA PKC

　　Objective It has been shown that sigma-1 receptor modulated many biological function and play an important role in neuron signal transmitter.Although Sigrma-1 receptor widely expressed in central nervous system and periphery, the modulation of neuron Na+ channel isoforms by sigma-1 receptor has not been examined in detail.The present study is to explore the mechanism of neuron Navl.2 channel modulation by sigma-1 receptor.Methods Here, we investigated the effects of (+)-SKF 10047, a sigma-1 receptor specific agonist, on rat Nav1.2 channel heterogenously expressed in human embryonic kidney cell line 293T ceils.The currents of Nav1.2 channel was recorded by whole-cell patch clamp.Results (1) 100 μM (+)-SKF 10047 significantly inhibits the Nav1.2 current by 40%.(+)-SKF 10047-induced inhibitory effect on rNaV1.2 current was fast and reversible.(2) In addition to inhibiting the rNav 1.2 current amplitude, (+)-SKF 10047 significantly accelerated the inactivation of rNav 1.2 channels and shifted the steady-state inactivation curve toward to hyperpolarizing potential.(3) BD 1047, a sigma-1 receptor antagonist reduced the inhibitory effect on rNav1.2 current induced by (+)-SKF10047.(4) Blocking PKA or PKC pathway by the conventional blockers H-89 or (G(o)6976) did not modified the effect of (+)-SKF10047 on rNaV1.2 current.(5) Inhibiting Gαs and Gαi with NF 449 and NF 023, or by cholera toxin (CTX) and pertussis toxin (PTX), also did not significantly changed the inhibitory effect of (+)-SKF10047 on rNaV1.2 current.Conclusion These results suggested that G-protein coupling receptor or PKA and PKC pathway was not associated with the effect of (+)-SKF10047 on rNav1.2 current.Whether the effect of (+)-SKF10047 on rNav1.2 current operate through sigma-1 receptor or channel protein interactions will require further investigations.