Trpm4 ion channels in pre-Bötzinger complex interneurons are essential for breathing motor pattern but not rhythm

PLoS Biology
Maria Cristina D PicardoC A Del Negro

Abstract

Inspiratory breathing movements depend on pre-Bötzinger complex (preBötC) interneurons that express calcium (Ca2+)-activated nonselective cationic current (ICAN) to generate robust neural bursts. Hypothesized to be rhythmogenic, reducing ICAN is predicted to slow down or stop breathing; its contributions to motor pattern would be reflected in the magnitude of movements (output). We tested the role(s) of ICAN using reverse genetic techniques to diminish its putative ion channels Trpm4 or Trpc3 in preBötC neurons in vivo. Adult mice transduced with Trpm4-targeted short hairpin RNA (shRNA) progressively decreased the tidal volume of breaths yet surprisingly increased breathing frequency, often followed by gasping and fatal respiratory failure. Mice transduced with Trpc3-targeted shRNA survived with no changes in breathing. Patch-clamp and field recordings from the preBötC in mouse slices also showed an increase in the frequency and a decrease in the magnitude of preBötC neural bursts in the presence of Trpm4 antagonist 9-phenanthrol, whereas the Trpc3 antagonist pyrazole-3 (pyr-3) showed inconsistent effects on magnitude and no effect on frequency. These data suggest that Trpm4 mediates ICAN, whose influence on frequency contradic...Continue Reading

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Citations

Mar 26, 2019·ELife·Jan-Marino Ramirez, Nathan A Baertsch
May 16, 2020·Frontiers in Cellular Neuroscience·Samuel BuntschuJürg Streit
May 3, 2020·Chaos·Yangyang Wang, Jonathan E Rubin
Nov 27, 2020·Frontiers in Cell and Developmental Biology·Boris LavanderosOscar Cerda
May 18, 2021·Frontiers in Neuroanatomy·Denise RiquelmeElias Leiva-Salcedo
Jun 3, 2021·International Journal of Molecular Sciences·Denise RiquelmeElias Leiva-Salcedo

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Methods Mentioned

BETA
PCR
confocal microscopy
Infrared Imaging

Key Resources (RRID) Mentioned

IMSR_JAX
AB_2040236
AB_880202
AB_2492288
AB_2340616
AB_2340437
AB
AB_2721181
AB_2687825

Software Mentioned

Quantasoft
Prism
Graphpad
LabChart

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