Zn(2+) enhancement of the recombinant 5-HT(3) receptor is modulated by divalent cations.
The modulation by Zn(2+) of recombinant murine 5-hydroxytryptamine(3A) (5-HT(3A)) receptor responses and its modification by Ca(2+) or Mg(2+) were studied using whole-cell voltage clamp and radioligand binding techniques. In the absence of other added divalent cations Zn(2+) enhanced the response to 5-HT by increasing maximum peak current (I(max)) to a maximum of 122.5%, decreasing the rate of desensitization (maximum t(1/2)=210%), and decreasing the EC(50) by approximately two fold. In the presence of Ca(2+) or Mg(2+), the effects of Zn(2+) on I(max) and t(1/2) were still manifest, although higher Zn(2+) concentrations were required; however, the effect on EC(50) was abolished. Zn(2+) also enhanced [3H]agonist but not [3H]antagonist binding. We propose there is more than one Zn(2+) binding site on the 5-HT(3) receptor molecule, and that one or more of these sites may also bind Ca(2+) and Mg(2+).
Hubbard
P C
PC
Division of Neurobiology, MRC Laboratory of Molecular Biology, Hills Road, Cambridge, UK.
Lummis
S C
SC
D002118:Calcium / Q000378:metabolism; D002412:Cations / Q000494:pharmacology; D002460:Cell Line; D004594:Electrophysiology; D006801:Humans; D007202:Indicators and Reagents; D007473:Ion Channels / Q000187:drug effects; D007668:Kidney / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism; D011869:Radioligand Assay; D011985:Receptors, Serotonin / Q000187:drug effects*; D044406:Receptors, Serotonin, 5-HT3; D011994:Recombinant Proteins / Q000187:drug effects; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D015032:Zinc / Q000494:pharmacology*
D002412:Cations; D007202:Indicators and Reagents; D007473:Ion Channels; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D011994:Recombinant Proteins; D017366:Serotonin Receptor Agonists; D008274:Magnesium; D015032:Zinc; D002118:Calcium