G-proteins modulate amiloride-sensitive sodium channels.
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.
Department of Medicine, University of Alabama at Birmingham 35294.
J K
JK
Bubien
R S
RS
Jope
D G
DG
Warnock
D000584:Amiloride / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D037342:Pertussis Toxin; D015398:Signal Transduction; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015222:Sodium Channels; D010566:Virulence Factors, Bordetella; D000584:Amiloride; D002772:Cholera Toxin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins