Bubien J K, Jope R S, Warnock D G
Department of Medicine, University of Alabama at Birmingham 35294.
J Biol Chem. 1994 Jul 8;269(27):17780-3.
We examined the regulation of an amiloride-sensitive sodium conductance expressed in human B lymphoid cells. This conductance was activated by two independent pathways, one involving cyclic adenylyl monophosphate (cAMP)-dependent protein kinase and the other involving a pertussis toxin-sensitive G-protein. Cholera toxin, presumably by increasing cellular cAMP, and pertussis toxin, which ADP-ribosylates certain GTP-binding proteins, both independently increased the amiloride-sensitive sodium conductance. Simultaneous treatment with both toxins, however, failed to increase the sodium conductance, implying that a single set of sodium channels was being affected by both toxins. In cells preactivated with pertussis toxin, 8-chlorophenylthio-cAMP inhibited the activated sodium conductance back to the basal level. Thus, cyclic AMP-dependent pathways can either activate or inhibit amiloride-sensitive sodium channels, depending upon the activation state of a pertussis toxin-sensitive GTP-binding protein. These findings support a hypothesis for the regulation of amiloride-sensitive sodium channels which incorporates the independent effects of cholera and pertussis toxins, and in which cyclic AMP can play a dual role in the regulation of channel activity.
我们研究了人B淋巴细胞中表达的一种氨氯地平敏感钠电导的调节机制。该电导可通过两条独立途径激活，一条涉及环磷酸腺苷（cAMP）依赖性蛋白激酶，另一条涉及百日咳毒素敏感的G蛋白。霍乱毒素大概是通过增加细胞内cAMP起作用，而百日咳毒素可使某些GTP结合蛋白发生ADP核糖基化，二者均可独立增加氨氯地平敏感钠电导。然而，同时用两种毒素处理却未能增加钠电导，这表明同一组钠通道受到了两种毒素的影响。在用百日咳毒素预激活的细胞中，8-氯苯硫基-cAMP可将激活的钠电导抑制至基础水平。因此，cAMP依赖性途径可激活或抑制氨氯地平敏感钠通道，具体取决于百日咳毒素敏感GTP结合蛋白的激活状态。这些发现支持了一种关于氨氯地平敏感钠通道调节的假说，该假说纳入了霍乱毒素和百日咳毒素的独立作用，并且在其中cAMP可在通道活性调节中发挥双重作用。
