G-PROTEINS MODULATE AMILORIDE-SENSITIVE SODIUM-CHANNELS

We examined the regulation of an amiloride-sensitive sodium conductanc e expressed in human B lymphoid cells. This conductance was activated by two independent pathways, one involving cyclic adenylyl monophospha te (cAMP)-dependent protein kinase and the other involving a pertussis toxin-sensitive G-protein. Cholera toxin, presumably by increasing ce llular cAMP, and pertussis toxin, which ADP-ribosylates certain GTP-bi nding proteins, both independently increased the amiloride-sensitive s odium conductance. Simultaneous treatment with both toxins, however, f ailed to increase the sodium conductance, implying that a single set o f sodium channels was being affected by both toxins. In cells preactiv ated with pertussis toxin, 8-chlorophenylthio-cAMP inhibited the activ ated sodium conductance back to the basal level. Thus, cyclic AMP-depe ndent pathways can either activate or inhibit amiloride-sensitive sodi um 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 incorpora tes the independent effects of cholera and pertussis toxins, and in wh ich cyclic AMP can play a dual role in the regulation of channel activ ity.