Connor J A, Hockberger P
J Physiol. 1984 Sep;354:139-62. doi: 10.1113/jphysiol.1984.sp015368.
Injection of cyclic AMP (cAMP) or cyclic GMP into identifiable neurones from several different gastropod species immediately depolarized the cell membranes in a dose-dependent manner. Doses were monitored photometrically and evidence is presented for depolarizing effects following nucleotide injections of as little as 30-35 mumol. The depolarizing effect was reversible and was demonstrated under voltage clamp to be primarily the result of a nucleotide-induced, transient increase in a membrane Na current, INa (cAMP). The charge-carrying species was identified by using ion-substituted salines, reversal potential in low-Na saline, and intracellular ion-sensitive electrode measurements. The current was resistant to tetrodotoxin, ouabain and amiloride. Substituting Trisma, tetramethylammonium or bis-tris propane for Na prevented the induced current, whereas Li substitution did not. Duration of the induced current was greatly prolonged in neurones bathed in the phosphodiesterase inhibitor isobutylmethylxanthine, or following injection of any of several cAMP analogues, indicating that the reversible nature of the current stems primarily from in situ hydrolysis of the injected dose and not current inactivation. Amplitude of the induced current either remained constant or decreased over the voltage range where it could be easily measured, i.e. -30 greater than Vm greater than -100 mV, reflecting a voltage as well as a chemical sensitivity of INa (cAMP).
向几种不同腹足纲动物的可识别神经元中注射环磷酸腺苷（cAMP）或环磷酸鸟苷（cGMP），细胞膜会立即以剂量依赖的方式去极化。通过光度法监测剂量，结果表明，注射低至30 - 35微摩尔的核苷酸后就会出现去极化效应。这种去极化效应是可逆的，并且在电压钳制下证明，主要是由于核苷酸诱导的膜钠电流INa（cAMP）瞬时增加所致。通过使用离子替代盐溶液、低钠盐溶液中的反转电位以及细胞内离子敏感电极测量来确定载流物质。该电流对河豚毒素、哇巴因和氨氯吡脒具有抗性。用Trisma、四甲基铵或双三羟甲基氨基甲烷替代钠可阻止诱导电流，而锂替代则不然。在浸泡于磷酸二酯酶抑制剂异丁基甲基黄嘌呤中的神经元中，或者在注射几种cAMP类似物中的任何一种后，诱导电流的持续时间会大大延长，这表明电流的可逆性主要源于注射剂量的原位水解，而非电流失活。在易于测量的电压范围内，即 - 30＞Vm＞ - 100 mV，诱导电流的幅度要么保持恒定，要么下降，这反映了INa（cAMP）对电压和化学物质的敏感性。
