In Vitro Pharmacological Modulation of PIEZO1 Channels in Frontal Cortex Neuronal Networks
PIEZO1 is a mechanosensitive ion channel expressed in various organs, including but not limited to the brain, heart, lungs, kidneys, bone, and skin. PIEZO1 has been implicated in astrocyte, microglia, capillary, and oligodendrocyte signaling in the mammalian cortex. Using murine embryonic frontal co...
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MDPI AG
2024-02-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/14/3/223 |
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| author | Pegah Haghighi Mandee K. Schaub Adam H. Shebindu Gayathri Vijayakumar Armaan Sood Rafael Granja-Vazquez Sourav S. Patnaik Caroline N. Jones Gregory O. Dussor Joseph J. Pancrazio |
| author_facet | Pegah Haghighi Mandee K. Schaub Adam H. Shebindu Gayathri Vijayakumar Armaan Sood Rafael Granja-Vazquez Sourav S. Patnaik Caroline N. Jones Gregory O. Dussor Joseph J. Pancrazio |
| author_sort | Pegah Haghighi |
| collection | DOAJ |
| description | PIEZO1 is a mechanosensitive ion channel expressed in various organs, including but not limited to the brain, heart, lungs, kidneys, bone, and skin. PIEZO1 has been implicated in astrocyte, microglia, capillary, and oligodendrocyte signaling in the mammalian cortex. Using murine embryonic frontal cortex tissue, we examined the protein expression and functionality of PIEZO1 channels in cultured networks leveraging substrate-integrated microelectrode arrays (MEAs) with additional quantitative results from calcium imaging and whole-cell patch-clamp electrophysiology. MEA data show that the PIEZO1 agonist Yoda1 transiently enhances the mean firing rate (MFR) of single units, while the PIEZO1 antagonist GsMTx4 inhibits both spontaneous activity and Yoda1-induced increase in MFR in cortical networks. Furthermore, calcium imaging experiments revealed that Yoda1 significantly increased the frequency of calcium transients in cortical cells. Additionally, in voltage clamp experiments, Yoda1 exposure shifted the cellular reversal potential towards depolarized potentials consistent with the behavior of PIEZO1 as a non-specific cation-permeable channel. Our work demonstrates that murine frontal cortical neurons express functional PIEZO1 channels and quantifies the electrophysiological effects of channel activation in vitro. By quantifying the electrophysiological effects of PIEZO1 activation in vitro, our study establishes a foundation for future investigations into the role of PIEZO1 in neurological processes and potential therapeutic applications targeting mechanosensitive channels in various physiological contexts. |
| first_indexed | 2024-04-24T18:29:17Z |
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| language | English |
| last_indexed | 2024-04-24T18:29:17Z |
| publishDate | 2024-02-01 |
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| series | Brain Sciences |
| spelling | doaj.art-a1d7566efb704def88c0fc06b7f9485e2024-03-27T13:28:41ZengMDPI AGBrain Sciences2076-34252024-02-0114322310.3390/brainsci14030223In Vitro Pharmacological Modulation of PIEZO1 Channels in Frontal Cortex Neuronal NetworksPegah Haghighi0Mandee K. Schaub1Adam H. Shebindu2Gayathri Vijayakumar3Armaan Sood4Rafael Granja-Vazquez5Sourav S. Patnaik6Caroline N. Jones7Gregory O. Dussor8Joseph J. Pancrazio9Department of Bioengineering, University of Texas at Dallas, Richardson, TX 75080, USADepartment of Neuroscience, University of Texas at Dallas, Richardson, TX 75080, USADepartment of Bioengineering, University of Texas at Dallas, Richardson, TX 75080, USADepartment of Neuroscience, University of Texas at Dallas, Richardson, TX 75080, USADepartment of Neuroscience, University of Texas at Dallas, Richardson, TX 75080, USACenter for Advanced Pain Studies, University of Texas at Dallas, Richardson, TX 75080, USADepartment of Bioengineering, University of Texas at Dallas, Richardson, TX 75080, USADepartment of Bioengineering, University of Texas at Dallas, Richardson, TX 75080, USADepartment of Neuroscience, University of Texas at Dallas, Richardson, TX 75080, USADepartment of Bioengineering, University of Texas at Dallas, Richardson, TX 75080, USAPIEZO1 is a mechanosensitive ion channel expressed in various organs, including but not limited to the brain, heart, lungs, kidneys, bone, and skin. PIEZO1 has been implicated in astrocyte, microglia, capillary, and oligodendrocyte signaling in the mammalian cortex. Using murine embryonic frontal cortex tissue, we examined the protein expression and functionality of PIEZO1 channels in cultured networks leveraging substrate-integrated microelectrode arrays (MEAs) with additional quantitative results from calcium imaging and whole-cell patch-clamp electrophysiology. MEA data show that the PIEZO1 agonist Yoda1 transiently enhances the mean firing rate (MFR) of single units, while the PIEZO1 antagonist GsMTx4 inhibits both spontaneous activity and Yoda1-induced increase in MFR in cortical networks. Furthermore, calcium imaging experiments revealed that Yoda1 significantly increased the frequency of calcium transients in cortical cells. Additionally, in voltage clamp experiments, Yoda1 exposure shifted the cellular reversal potential towards depolarized potentials consistent with the behavior of PIEZO1 as a non-specific cation-permeable channel. Our work demonstrates that murine frontal cortical neurons express functional PIEZO1 channels and quantifies the electrophysiological effects of channel activation in vitro. By quantifying the electrophysiological effects of PIEZO1 activation in vitro, our study establishes a foundation for future investigations into the role of PIEZO1 in neurological processes and potential therapeutic applications targeting mechanosensitive channels in various physiological contexts.https://www.mdpi.com/2076-3425/14/3/223PIEZO1 channelsPIEZO1 antagonist GsMTx4calcium imagingcortical neuronsextracellular recordingmechanosensitive |
| spellingShingle | Pegah Haghighi Mandee K. Schaub Adam H. Shebindu Gayathri Vijayakumar Armaan Sood Rafael Granja-Vazquez Sourav S. Patnaik Caroline N. Jones Gregory O. Dussor Joseph J. Pancrazio In Vitro Pharmacological Modulation of PIEZO1 Channels in Frontal Cortex Neuronal Networks Brain Sciences PIEZO1 channels PIEZO1 antagonist GsMTx4 calcium imaging cortical neurons extracellular recording mechanosensitive |
| title | In Vitro Pharmacological Modulation of PIEZO1 Channels in Frontal Cortex Neuronal Networks |
| title_full | In Vitro Pharmacological Modulation of PIEZO1 Channels in Frontal Cortex Neuronal Networks |
| title_fullStr | In Vitro Pharmacological Modulation of PIEZO1 Channels in Frontal Cortex Neuronal Networks |
| title_full_unstemmed | In Vitro Pharmacological Modulation of PIEZO1 Channels in Frontal Cortex Neuronal Networks |
| title_short | In Vitro Pharmacological Modulation of PIEZO1 Channels in Frontal Cortex Neuronal Networks |
| title_sort | in vitro pharmacological modulation of piezo1 channels in frontal cortex neuronal networks |
| topic | PIEZO1 channels PIEZO1 antagonist GsMTx4 calcium imaging cortical neurons extracellular recording mechanosensitive |
| url | https://www.mdpi.com/2076-3425/14/3/223 |
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