TY - JOUR
T1 - G-proteins modulate amiloride-sensitive sodium channels
AU - Bubien, James K.
AU - Jope, Richard S.
AU - Warnock, David G.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1994/7/8
Y1 - 1994/7/8
N2 - 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.
AB - 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.
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M3 - Article
C2 - 8027031
AN - SCOPUS:0028228345
VL - 269
SP - 17780
EP - 17783
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 27
ER -