Copper Increases the Cooperative Gating of Rat P2X2a Receptor Channels
<b>Background/Objectives:</b> P2X receptor channels are widely expressed in the CNS, where they have multiple functions in health and disease. The rat P2X2a (rP2X2a) receptor channel is modulated by copper, an essential trace element that plays important roles in synaptic modulation and...
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MDPI AG
2024-11-01
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| author | Elias Leiva-Salcedo Denise Riquelme Juan Pablo Huidobro-Toro Claudio Coddou |
| author_facet | Elias Leiva-Salcedo Denise Riquelme Juan Pablo Huidobro-Toro Claudio Coddou |
| author_sort | Elias Leiva-Salcedo |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> P2X receptor channels are widely expressed in the CNS, where they have multiple functions in health and disease. The rat P2X2a (rP2X2a) receptor channel is modulated by copper, an essential trace element that plays important roles in synaptic modulation and neurodegenerative disorders. Although essential extracellular amino acids that coordinate copper have been identified, the exact mechanism of copper-induced modulation has not been yet elucidated. <b>Methods</b>: We used HEK293T cells expressing rP2X2a channel(s) and performed outside-out single-channel and whole-cell recordings to explore copper’s effects on rP2X2 currents and determine whether this metal can increase the cooperative gating of rP2X2a channel. <b>Results</b>: In whole-cell recordings and in patches containing 2 or 3 rP2X2a channels, copper enhanced the ATP-induced currents, significantly reducing the ATP EC<sub>50</sub> and increasing the Hill coefficient. Moreover, copper increased the apparent P<sub>o</sub> in patches containing two or three channels. By contrast, in patches containing only one rP2X2a channel, we did not observe any significant changes in ATP EC<sub>50</sub>, the Hill coefficient, or P<sub>o</sub>. <b>Conclusions</b>: Copper modulates the gating of rP2X2a channels, enhancing interchannel cooperativity without altering single-channel conductance or P<sub>o</sub>. This novel regulatory mechanism could be relevant for understanding the role of P2X2 channels in physiological and pathological processes. |
| format | Article |
| id | doaj-art-ed6e788264fb434f923985d9b8bb391c |
| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
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| series | Pharmaceuticals |
| spelling | doaj-art-ed6e788264fb434f923985d9b8bb391c2024-12-27T14:45:47ZengMDPI AGPharmaceuticals1424-82472024-11-011712159010.3390/ph17121590Copper Increases the Cooperative Gating of Rat P2X2a Receptor ChannelsElias Leiva-Salcedo0Denise Riquelme1Juan Pablo Huidobro-Toro2Claudio Coddou3Department of Biology, Faculty of Chemistry and Biology, Universidad de Santiago de Chile, Santiago 9170022, ChileDepartment of Biology, Faculty of Chemistry and Biology, Universidad de Santiago de Chile, Santiago 9170022, ChileDepartment of Biology, Faculty of Chemistry and Biology, Universidad de Santiago de Chile, Santiago 9170022, ChileDepartamento de Ciencias Biomédicas, Facultad de Medicina, Universidad Católica del Norte, Coquimbo 1781421, Chile<b>Background/Objectives:</b> P2X receptor channels are widely expressed in the CNS, where they have multiple functions in health and disease. The rat P2X2a (rP2X2a) receptor channel is modulated by copper, an essential trace element that plays important roles in synaptic modulation and neurodegenerative disorders. Although essential extracellular amino acids that coordinate copper have been identified, the exact mechanism of copper-induced modulation has not been yet elucidated. <b>Methods</b>: We used HEK293T cells expressing rP2X2a channel(s) and performed outside-out single-channel and whole-cell recordings to explore copper’s effects on rP2X2 currents and determine whether this metal can increase the cooperative gating of rP2X2a channel. <b>Results</b>: In whole-cell recordings and in patches containing 2 or 3 rP2X2a channels, copper enhanced the ATP-induced currents, significantly reducing the ATP EC<sub>50</sub> and increasing the Hill coefficient. Moreover, copper increased the apparent P<sub>o</sub> in patches containing two or three channels. By contrast, in patches containing only one rP2X2a channel, we did not observe any significant changes in ATP EC<sub>50</sub>, the Hill coefficient, or P<sub>o</sub>. <b>Conclusions</b>: Copper modulates the gating of rP2X2a channels, enhancing interchannel cooperativity without altering single-channel conductance or P<sub>o</sub>. This novel regulatory mechanism could be relevant for understanding the role of P2X2 channels in physiological and pathological processes.https://www.mdpi.com/1424-8247/17/12/1590cooperativityP2X2P2X2asingle channelcoppertrace metals |
| spellingShingle | Elias Leiva-Salcedo Denise Riquelme Juan Pablo Huidobro-Toro Claudio Coddou Copper Increases the Cooperative Gating of Rat P2X2a Receptor Channels Pharmaceuticals cooperativity P2X2 P2X2a single channel copper trace metals |
| title | Copper Increases the Cooperative Gating of Rat P2X2a Receptor Channels |
| title_full | Copper Increases the Cooperative Gating of Rat P2X2a Receptor Channels |
| title_fullStr | Copper Increases the Cooperative Gating of Rat P2X2a Receptor Channels |
| title_full_unstemmed | Copper Increases the Cooperative Gating of Rat P2X2a Receptor Channels |
| title_short | Copper Increases the Cooperative Gating of Rat P2X2a Receptor Channels |
| title_sort | copper increases the cooperative gating of rat p2x2a receptor channels |
| topic | cooperativity P2X2 P2X2a single channel copper trace metals |
| url | https://www.mdpi.com/1424-8247/17/12/1590 |
| work_keys_str_mv | AT eliasleivasalcedo copperincreasesthecooperativegatingofratp2x2areceptorchannels AT deniseriquelme copperincreasesthecooperativegatingofratp2x2areceptorchannels AT juanpablohuidobrotoro copperincreasesthecooperativegatingofratp2x2areceptorchannels AT claudiocoddou copperincreasesthecooperativegatingofratp2x2areceptorchannels |