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TRPM4 mediates a subthreshold membrane potential oscillation in respiratory chemoreceptor neurons that drives pacemaker firing and breathing.
- Source :
-
Cell reports [Cell Rep] 2021 Feb 02; Vol. 34 (5), pp. 108714. - Publication Year :
- 2021
-
Abstract
- Brainstem networks that control regular tidal breathing depend on excitatory drive, including from tonically active, CO <subscript>2</subscript> /H <superscript>+</superscript> -sensitive neurons of the retrotrapezoid nucleus (RTN). Here, we examine intrinsic ionic mechanisms underlying the metronomic firing activity characteristic of RTN neurons. In mouse brainstem slices, large-amplitude membrane potential oscillations are evident in synaptically isolated RTN neurons after blocking action potentials. The voltage-dependent oscillations are abolished by sodium replacement; blocking calcium channels (primarily L-type); chelating intracellular Ca <superscript>2+</superscript> ; and inhibiting TRPM4, a Ca <superscript>2+</superscript> -dependent cationic channel. Likewise, oscillation voltage waveform currents are sensitive to calcium and TRPM4 channel blockers. Extracellular acidification and serotonin (5-HT) evoke membrane depolarization that augments TRPM4-dependent oscillatory activity and action potential discharge. Finally, inhibition of TRPM4 channels in the RTN of anesthetized mice reduces central respiratory output. These data implicate TRPM4 in a subthreshold oscillation that supports the pacemaker-like firing of RTN neurons required for basal, CO <subscript>2</subscript> -stimulated, and state-dependent breathing.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 34
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 33535052
- Full Text :
- https://doi.org/10.1016/j.celrep.2021.108714