ATP modulates the function of inositol 1,4,5-trisphosphate-gated channels at two sites.
The inositol 1,4,5-trisphosphate (IP3) receptor, a Ca(2+)-permeable channel, plays a key role in intracellular Ca2+ signaling. The effects of ATP on the IP3 receptor at the single-channel level were characterized after channel incorporation into planar lipid bilayers. ATP alone was not sufficient to open the IP3-gated channel, but addition of ATP or nonhydrolyzable ATP analogs in the presence of IP3 increased the frequency of channel openings 4.8-fold and increased the average duration of channel openings 2.5-fold; channel conductance was unchanged. High concentrations of ATP (> 4 mM) decreased channel activity most probably by competing with IP3-binding site. Allosteric modulation of IP3-induced Ca2+ release by ATP may contribute to the maintenance of cell viability during periods of energy starvation.
Bezprozvanny
I
I
Department of Medicine, University of Connecticut, Farmington 06030.
Ehrlich
B E
BE
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels; D002531:Cerebellum / Q000502:physiology*; D004285:Dogs; D004721:Endoplasmic Reticulum / Q000502:physiology*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism / Q000494:pharmacology*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008051:Lipid Bilayers; D008433:Mathematics; D008861:Microsomes / Q000502:physiology*; D008959:Models, Neurological; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear; D015398:Signal Transduction / Q000502:physiology
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007473:Ion Channels; D008051:Lipid Bilayers; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D002118:Calcium