Eigen RadarScience
Archive
Analysis

TMEM63B loss delays mice’s escape from harmful heat

Mice lacking the TMEM63B ion channel responded more slowly to harmful heat in a peer-reviewed study. Measurements in sensory neurons and cultured cells connect the protein to heat detection and show that membrane lipids can change its response. The finding concerns a protective sensory system in animals; effects on chronic pain or treatment safety in people were not tested.

Science··Evening
A brown laboratory mouse faces away from a smooth metal platform inside a clear testing enclosure.

Heat withdrawal slows when the channel is absent

Mice without TMEM63B, a protein channel that lets ions cross cell membranes, withdrew more slowly from harmful heat in a peer-reviewed study published on 16 October. The result adds a component to the network of sensors that turns dangerous temperatures into a protective response. The experiments concern animals and cultured cells, with no human treatment trial.[1], [2]

Researchers removed the gene throughout the body and, separately, in sensory ganglia: groups of nerve cells near the spinal cord that receive information from the body. Both approaches helped investigate the channel’s contribution to heat sensation. Tests of mechanical and cold stimuli did not show the same pattern of impairment.[1]

The channel is present in several types of sensory neuron. Its absence did not change the number or distribution of the neurons examined, pointing toward a change in their function rather than their development. The cell measurements therefore examine how these existing neurons respond to heat.[1], [2]

Nerve-cell measurements follow the behavioural change

Heat also elicited smaller calcium responses and altered electrical activity in sensory neurons lacking the protein. Under some heating conditions, fewer cells responded and the threshold for firing rose. Heat sensation nevertheless persisted, leaving room for other channels, residual protein and central nervous system contributions within this sensory pathway.[1]

In a separate reconstructed cell system, the channel’s response to heating was modest until researchers added arachidonic acid, a lipid involved in membranes and cellular signalling. This sensitized the response. The substance did not act as a strong direct opener at room temperature, and a non-metabolizable analogue supported an effect beyond its breakdown products alone.[1]

The membrane environment changes the response

The arachidonic-acid concentration exceeded normal free cellular levels. Its physiological counterpart therefore remains uncertain, and the experiments did not separate direct binding to TMEM63B from changes in membrane properties. Those distinctions matter for explaining how a channel already associated with physical changes in cells participates in temperature sensing.[1]

The behavioural work used relatively small mouse groups. Removing a gene cannot establish the effects of a selective, reversible medicine. Chronic-pain benefit, a therapeutic dose and long-term safety were not measured. A slower withdrawal can also mean delayed detection of danger, so the observed sensory change carries a protective function as well as a connection to pain.[1]

For more information on this topic, you can read the related columns.

References

  1. News sourcePLOS BiologyTMEM63B contributes to sensing harmful heat in mice↩1↩2↩3↩4↩5↩6↩7
  2. News sourceCiencias.uyTMEM63B adds evidence on sensing painful heat↩1↩2
Space and explorationEnergy transition and climate

More analysis from this desk

View all Brief analyses from the Science desk →