| First Author | Bos R | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 6815 |
| PubMed ID | 34819493 | Mgi Jnum | J:315176 |
| Mgi Id | MGI:6830747 | Doi | 10.1038/s41467-021-27113-x |
| Citation | Bos R, et al. (2021) Trpm5 channels encode bistability of spinal motoneurons and ensure motor control of hindlimbs in mice. Nat Commun 12(1):6815 |
| abstractText | Bistable motoneurons of the spinal cord exhibit warmth-activated plateau potential driven by Na(+) and triggered by a brief excitation. The thermoregulating molecular mechanisms of bistability and their role in motor functions remain unknown. Here, we identify thermosensitive Na(+)-permeable Trpm5 channels as the main molecular players for bistability in mouse motoneurons. Pharmacological, genetic or computational inhibition of Trpm5 occlude bistable-related properties (slow afterdepolarization, windup, plateau potentials) and reduce spinal locomotor outputs while central pattern generators for locomotion operate normally. At cellular level, Trpm5 is activated by a ryanodine-mediated Ca(2+) release and turned off by Ca(2+) reuptake through the sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) pump. Mice in which Trpm5 is genetically silenced in most lumbar motoneurons develop hindlimb paresis and show difficulties in executing high-demanding locomotor tasks. Overall, by encoding bistability in motoneurons, Trpm5 appears indispensable for producing a postural tone in hindlimbs and amplifying the locomotor output. |
