| First Author | Li K | Year | 2021 |
| Journal | Cell Rep | Volume | 34 |
| Issue | 5 | Pages | 108714 |
| PubMed ID | 33535052 | Mgi Jnum | J:320838 |
| Mgi Id | MGI:6716789 | Doi | 10.1016/j.celrep.2021.108714 |
| Citation | Li K, et al. (2021) TRPM4 mediates a subthreshold membrane potential oscillation in respiratory chemoreceptor neurons that drives pacemaker firing and breathing. Cell Rep 34(5):108714 |
| abstractText | Brainstem networks that control regular tidal breathing depend on excitatory drive, including from tonically active, CO2/H(+)-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(2+); and inhibiting TRPM4, a Ca(2+)-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, CO2-stimulated, and state-dependent breathing. |
