布格呋喃抗焦虑及抑郁作用的电生理机制

陈春林; 王伟平; 王 玲; 王晓良

布格呋喃抗焦虑及抑郁作用的电生理机制

Electrophysiology mechanisms of 4-butyl-alpha-agarofuran: a new anxiolytic and antidepressant drug

摘要

摘要:
研究布格呋喃 (AF-5) 抗焦虑及抑郁作用的电生理学机制。采用全细胞膜片钳技术, 观察AF-5对原代培养大鼠皮层神经元上电压依赖性钠离子通道、电压依赖性钾离子通道、电压依赖性L-型钙离子通道、γ-氨基丁酸 (GABA) 依赖的氯离子通道以及稳定转染于HEK293细胞系上Kv2.1通道电流的影响。结果表明, AF-5能明显抑制原代培养大鼠皮层神经元上电压依赖性延迟整流钾电流 (I_K(DR))、L-型钙通道电流 (I_L-Ca) 以及稳定转染于HEK293细胞系上Kv2.1通道电流, 其IC₅₀分别为6.17、4.4和5.29 μmol·L⁻¹, 但对电压依赖性钠通道电流 (I_Na)、瞬时外向钾电流 (I_K(A)) 以及GABA介导的氯离子通道电流的抑制作用较弱。研究表明, AF-5的抗焦虑及抑郁作用可能与其抑制以Kv2.1为主的神经元I_K(DR)及I_L-Ca有关。

Abstract:
To investigate the electrophysiology mechanisms of new anxiolytic and antidepressant drug: 4- butyl-alpha-agarofuran (AF-5), patch clamp-recording was used to test the effects of AF-5 on voltage-dependent sodium currents, voltage-dependent potassium currents, L-type voltage-dependent calcium currents and GABA dependent Cl⁻ currents in primary cultured rat cortical neurons. Effects of AF-5 on Kv2.1 currents, expressed stably in HEK293 cells, were also tested. Our results showed that, delayed rectifier potassium currents (I_K(DR)), L-type voltage-dependent calcium currents (I_L-Ca) in primary cultured rat cortical neurons and Kv2.1 currents in HEK293 cells were significantly inhibited by AF-5, with IC₅₀ as 6.17, 4.4 and 5.29 μmol·L⁻¹ respectively. However, voltage-dependent sodium currents (I_Na), GABA dependent Cl⁻ currents and transient outward potassium currents (I_K(A)) in primary cultured rat cortical neurons were not significantly blocked by AF-5. Our results concluded that, blocked I_K(DR) and I_L-Ca currents may be one of the mechanisms of anxiolytic and antidepression actions of AF-5.

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