Zn2+ potentiates ATP-activated currents in rat sympathetic neurons.
The ATP-activated inward current (IATP) in cultured rat superior cervical ganglion neurons and its modulation by extracellular Zn2+ were examined. ATP activated a non-specific cation conductance and caused a transient rise in intracellular Ca2+. The current response was specifically activated by ATP and was blocked by the P2-purinoceptor antagonist, suramin. Low concentrations of extracellular Zn2+ rapidly and reversibly potentiated both IATP and the intracellular Ca2+ rise. The potentiation by 10 microM Zn2+ was dependent on the concentration of agonist; Zn2+ increased the sensitivity of activation without potentiating the maximum response. Higher concentrations of Zn2+ reduced and prolonged the current, consistent with open-channel block. We hypothesize that there exist two sites of action for Zn2+: a positively acting allosteric site that enhances current amplitude and a site, possibly within the pore, that blocks conductance through the channel.
Cloues
R
R
Department of Pharmacology, University College London, UK.
Jones
S
S
Brown
D A
DA
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002413:Cations, Divalent / Q000494:pharmacology; D002478:Cells, Cultured; D004594:Electrophysiology; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000187:drug effects; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015032:Zinc / Q000494:pharmacology*
D002413:Cations, Divalent; D007473:Ion Channels; D018048:Receptors, Purinergic P2; D013498:Suramin; D000255:Adenosine Triphosphate; D015032:Zinc; D002118:Calcium