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Updated: Jul 6, 2026

Proteomics to Identify Proteins Interacting with P2X2 Ligand-Gated Cation Channels
Published on: May 18, 2009
P2Y(1) receptor modulation of endogenous ion channel function in Xenopus oocytes: Involvement of transmembrane
So Yeong Lee1, Robert A Nicholas, Scott M O'Grady
1Department of Physiology and Molecular Veterinary Biosciences Graduate Program, University of Minnesota, St. Paul, Minnesota, USA.
Abstract:
Agonist activation of the hP2Y(1) receptor expressed in Xenopus oocytes stimulated an endogenous voltage-gated ion channel, previously identified as the transient inward (T(in)) channel. When human P2Y(1) (hP2Y(1)) and skate P2Y (sP2Y) receptors were expressed in Xenopus oocytes, time-to-peak values (a measure of the response to membrane hyperpolarization) of the T(in) channel were significantly reduced compared to oocytes expressing the hB(1)-bradykinin receptor or the rat M(1)-muscarinic (rM(1)) receptor. Differences in activation were also observed in the T(in) currents elicited by various P2Y receptor subtypes. The time-to-peak values of the T(in) channel in oocytes expressing the hP2Y(4), hP2Y(11), or hB(1)-bradykinin receptors were similar, whereas the channel had significantly shorter time-to-peak values in oocytes expressing either the hP2Y(1) or sP2Y receptor. Amino acid substitutions at His-132, located in the third transmembrane domain (TM3) of the hP2Y(1) receptor, delayed the onset of channel opening, but not the kinetics of the activation process. In addition, Zn(2+) sensitivity was also dependent on the subtype of P2Y receptor expressed. Replacement of His-132 in the hP2Y(1) receptor with either Ala or Phe increased Zn(2+) sensitivity of the T(in) current. In contrast, truncation of the C-terminal region of the hP2Y(1) receptor had no affect on activation or Zn(2+) sensitivity of the T(in) channel. These results suggested that TM3 in the hP2Y(1) receptor was involved in modulating ion channel function and blocker pharmacology of the T(in) channel.
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