Cannabinoids modulate voltage sensitive potassium A-current in hippocampal neurons via a cAMP-dependent process.
Cannabinoids modulate voltage sensitive potassium A-current in hippocampal neurons via a cAMP-dependent process.
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发表时间：
1995-05
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通讯作者：
S. Deadwyler;R. Hampson;J. Mu;A. Whyte;S. Childers
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作者：
S. Deadwyler;R. Hampson;J. Mu;A. Whyte;S. Childers
先前的研究表明，大麻素受体类似物增加培养的海马细胞中的电压依赖性钾A电流（IA）。由于大麻素受体抑制腺苷酸环化酶，本研究探讨了cAMP是否在介导IA的这种作用中发挥了作用。研究了大麻素受体对电压依赖性IA的调节是否通过cAMP依赖性过程起作用的具体问题。cAMP类似物，8-溴-cAMP，以及腺苷酸环化酶兴奋剂毛喉素，产生浓度依赖性的变化，IA的大麻素受体配体所产生的相反。此外，磷酸二酯酶抑制剂3-异丁基-1-甲基黄嘌呤也产生了一个显着的负移的稳态电压依赖性IA和增加的影响forskolin对IA。如先前的研究所示，大麻素激动剂WIN 55，212 -2通过降低IA的稳态电压依赖性失活来增加IA。WIN 55，212 -2也逆转了毛喉素对IA的作用。电生理学研究通过直接测定这些细胞中的cAMP来进行，其中大麻素以百日咳毒素敏感的方式抑制毛喉素刺激的cAMP达50%。结果证实，百日咳毒素敏感的大麻素受体介导的IA的变化可能是腺苷酸环化酶抑制的结果。研究结果进行了讨论，通过大麻素受体介导的抑制细胞内的cAMP水平的IA电导特性的调制。
Previous studies have shown that cannabinoid receptor analogs increase voltage-dependent potassium A-current (IA) in cultured hippocampal cells. Because cannabinoid receptors inhibit adenylate cyclase, the present study explored whether cAMP played a role in mediating this effect on IA. The specific issue of whether cannabinoid receptor modulation of voltage-dependent IA acts via a cAMP-dependent process was investigated. The cAMP analog, 8-bromo-cAMP, as well as the adenylate cyclase stimulant forskolin, produced concentration-dependent shifts in IA that were opposite those produced by cannabinoid receptor ligands. Moreover, the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine also produced a marked negative shift in the steady-state voltage dependence of IA and increased the effect of forskolin on IA. As shown in previous studies, the cannabinoid agonist WIN 55,212-2 increased IA via a decrease in steady-state voltage-dependent inactivation of IA. WIN 55,212-2 also reversed the effects of forskolin on IA. The electrophysiological studies were paralleled by direct assays of cAMP in these cells, where cannabinoids inhibited forskolin-stimulated cAMP by 50% in a pertussis toxin-sensitive manner. The results confirmed that pertussis toxin-sensitive cannabinoid receptor-mediated changes in IA were probably the result of inhibition of adenylate cyclase. The findings are discussed in terms of modulation of IA conductance properties via cannabinoid receptor-mediated inhibition of cAMP levels within the cell.