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BRIEF RESEARCH REPORT article

Front. Cell Dev. Biol.
Sec. Membrane Traffic
Volume 12 - 2024 | doi: 10.3389/fcell.2024.1440140

Cholinergic stimulation stabilizes TRPM4 in the plasma membrane of cortical pyramidal neurons

Provisionally accepted
Paula Leyton Paula Leyton Denise Riquelme Denise Riquelme *Francisco A. Peralta Francisco A. Peralta Franco D. Navarro Franco D. Navarro Elias Leiva-Salcedo Elias Leiva-Salcedo *
  • Laboratorio de Sistemas Neurales, Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago, Santiago, Chile

The final, formatted version of the article will be published soon.

    TRPM4 is a calcium activated non-selective cation channel, impermeable to Ca2+, in neurons it has been implicated in the regulation of the excitability and in the persistent firing. Cholinergic stimulation is also implicated in changes in excitability that leads neurons to an increased firing frequency, however it is not clear whether TRPM4 is involved in the cholinergic-induced increase in firing frequency. Here using a combination of patch clamp electrophysiology, Ca2+ imaging, immunofluorescence, fluorescence recovery after photobleaching (FRAP) and pharmacological approach, we demonstrate that carbachol (Cch) increases firing frequency, intracellular Ca2+ and that TRPM4 inhibition using 9-Ph and CBA reduces firing frequency and decreases the peak in intracellular Ca2+ induced by Cch in cortical pyramidal neurons in culture. Moreover, we determined that cholinergic stimulation reduces TRPM4 recycling and stabilizes TRPM4 in the plasma membrane. Together our results indicate that cholinergic stimulation increases firing in a TRPM4 dependent manner, and also increases the TRPM4 stability in the membrane, suggesting that TRPM4 is locked in microdomains in the membrane, possibly signaling or cytoskeleton proteins complexes

    Keywords: TRPM4, traffic, cortical neuron, FRAP, cholinergic

    Received: 29 May 2024; Accepted: 03 Jul 2024.

    Copyright: © 2024 Leyton, Riquelme, Peralta, Navarro and Leiva-Salcedo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Denise Riquelme, Laboratorio de Sistemas Neurales, Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago, Santiago, Chile
    Elias Leiva-Salcedo, Laboratorio de Sistemas Neurales, Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago, Santiago, Chile

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