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TRPM4 inhibition slows neuritogenesis progression of cortical neurons
Denise Riquelme1, Nicole Juanchuto-Viertel1, Carlos Álamos1
1Department of Biology, Faculty of Chemistry and Biology, University of Santiago of Chile, Santiago, Chile.
Abstract:
TRPM4 is a non-selective cation channel activated by intracellular Ca2+ but only permeable to monovalent cations, its activation regulates membrane potential and intracellular calcium. This channel participates in the migration and adhesion of non-excitable cells and forms an integral part of the focal adhesion complex. In neurons, TRPM4 expression starts before birth and its function at this stage is not clear, but it may function in processes such as neurite development. Here we investigate the role of TRPM4 in neuritogenesis. We found that neurons at DIV 0 express TRPM4, the inhibition of TRPM4 using 9-Ph reduces neurite number and slows the progression of neurite development, keeping neurons in stage 1. The genetic suppression of TRPM4 using an shRNA at later stages (DIV2) reduces neurite length. Conversely, at DIV 0, TRPM4 inhibition augments the Cch-induced Ca2 + i increase, altering the calcium homeostasis. Together, these results show that TRPM4 participates in progression of neurite development and suggest a critical role of the calcium modulation during this stage of neuronal development.
Insights
Transient Receptor Potential Melastatin 4 (TRPM4) channels are crucial for neurite development. Inhibiting TRPM4 in developing neurons impairs neurite growth and alters calcium homeostasis, highlighting its role in neuronal development.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Transient Receptor Potential Melastatin 4 (TRPM4) is a cation channel involved in non-excitable cell functions.
- TRPM4 expression in neurons begins prenatally, but its role in neuronal development, specifically neuritogenesis, remains unclear.
Purpose of the Study:
- To investigate the role of TRPM4 in neurite development and calcium homeostasis in developing neurons.
Main Methods:
- Utilized TRPM4 inhibition with 9-Ph and genetic suppression via shRNA in cultured neurons at different developmental stages (DIV 0 and DIV 2).
- Assessed neurite number, neurite development progression, and Cch-induced intracellular calcium (Ca2+i) increases.
Main Results:
- TRPM4 inhibition at DIV 0 reduced neurite number and slowed development, arresting neurons in stage 1.
- Genetic suppression of TRPM4 at DIV 2 decreased neurite length.
- TRPM4 inhibition at DIV 0 augmented Cch-induced Ca2+i increases, disrupting calcium homeostasis.
Conclusions:
- TRPM4 plays a significant role in the progression of neurite development.
- Calcium modulation by TRPM4 is critical during early neuronal development stages.
