Enhanced excitability of cortical neurons in low-divalent solutions is primarily mediated by altered voltage-dependence of voltage-gated sodium channels
| Autor: | Stephen M. Smith, Briana J Martiszus, Wenhan Chang, Timur Tsintsadze |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male surface charge Mouse QH301-705.5 Science chemistry.chemical_element Action Potentials Gating Voltage-Gated Sodium Channels Calcium General Biochemistry Genetics and Molecular Biology Divalent 03 medical and health sciences Mice 0302 clinical medicine excitability Extracellular medicine CaSR Animals Biology (General) Cells Cultured chemistry.chemical_classification Membrane potential Neurons calcium General Immunology and Microbiology NALCN General Neuroscience Sodium channel Depolarization General Medicine Mice Inbred C57BL VGSC 030104 developmental biology medicine.anatomical_structure chemistry Biophysics Medicine Female Neuron Ion Channel Gating Receptors Calcium-Sensing 030217 neurology & neurosurgery Research Article Neuroscience |
| Zdroj: | eLife eLife, Vol 10 (2021) |
| ISSN: | 2050-084X |
| Popis: | Increasing extracellular [Ca2+] ([Ca2+]o) strongly decreases intrinsic excitability in neurons but the mechanism is unclear. By one hypothesis, [Ca2+]o screens surface charge, reducing voltage-gated sodium channel (VGSC) activation and by another [Ca2+]o activates Calcium-sensing receptor (CaSR) closing the sodium-leak channel (NALCN). Here we report that neocortical neurons from CaSR-deficient (Casr-/-) mice had more negative resting potentials and did not fire spontaneously in reduced divalent-containing solution (T0.2) in contrast with wild-type (WT). However, after setting membrane potential to −70 mV, T0.2 application similarly depolarized and increased action potential firing in Casr-/- and WT neurons. Enhanced activation of VGSCs was the dominant contributor to the depolarization and increase in excitability by T0.2 and occurred due to hyperpolarizing shifts in VGSC window currents. CaSR deletion depolarized VGSC window currents but did not affect NALCN activation. Regulation of VGSC gating by external divalents is the key mechanism mediating divalent-dependent changes in neocortical neuron excitability. |
| Databáze: | OpenAIRE |
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