title: Interaction of luminal calcium and cytosolic ATP in the control of type 1 inositol (1,4,5)-trisphosphate receptor channels.
abstract: Ca(2+) within intracellular stores (luminal Ca(2+)) is believed to play a role in regulating Ca(2+) release into the cytosol via the inositol (1,4,5)-trisphosphate (Ins(1,4,5)P(3))-gated Ca(2+) channel (or Ins(1,4,5)P(3) receptor). To investigate this, we incorporated purified Type 1 Ins(1,4,5)P(3) receptor from rat cerebellum into planar lipid bilayers and monitored effects at altered luminal [Ca(2+)] using K(+) as the current carrier. At a high luminal [Ca(2+)] and in the presence of optimal [Ins(1,4,5)P(3)] and cytosolic [Ca(2+)], a short burst of Ins(1,4,5)P(3) receptor channel activity was followed by complete inactivation. Lowering the luminal [Ca(2+)] caused the channel to reactivate indefinitely. At luminal [Ca(2+)], reflecting a partially empty store, channel activity did not inactivate. The addition of cytosolic ATP to a channel inactivated by high luminal [Ca(2+)] caused reactivation. We provide evidence that luminal Ca(2+) is exerting its effects via a direct interaction with the luminal face of the receptor. Activation of the receptor by ATP may act as a device by which cytosolic Ca(2+) overload is prevented when the energy state of the cell is compromised.
authors.affiliation: School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, United Kingdom.
authors.forename: E C
authors.initials: EC
authors.lastname: Thrower
authors.forename: H
authors.initials: H
authors.lastname: Mobasheri
authors.forename: S
authors.initials: S
authors.lastname: Dargan
authors.forename: P
authors.initials: P
authors.lastname: Marius
authors.forename: E J
authors.initials: EJ
authors.lastname: Lea
authors.forename: A P
authors.initials: AP
authors.lastname: Dawson
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002531:Cerebellum; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D004553:Electric Conductivity; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors; D015640:Ion Channel Gating / Q000187:drug effects; D008051:Lipid Bilayers / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D011510:Proteolipids / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008051:Lipid Bilayers; D011510:Proteolipids; D018160:Receptors, Cytoplasmic and Nuclear; C020485:proteoliposomes; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D011188:Potassium; D002118:Calcium