The TRPM2 ion channel is required for sensitivity to warmth

Area of Science:

• Neuroscience
• Sensory Biology
• Molecular Physiology

Background:

• Thermally activated ion channels, including Transient Receptor Potential (TRP) channels, mediate thermosensation across various temperature ranges.
• Known channels like TRPV1, TRPV2, TRPV3, TRPV4, TRPM3, TRPM8, and TRPA1 are implicated in detecting heat and cold, but the mechanism for non-painful warmth detection remains unclear.
• Genetic deletion studies in mice reveal modest effects on thermal behavior, except for TRPM8's significant impact on coolness perception.

Purpose of the Study:

• To identify the molecular mechanism responsible for detecting non-painful warmth.
• To investigate the role of TRPM2 in thermosensation and thermal behavior.

Main Methods:

• Utilized calcium imaging to identify thermally sensitive somatosensory neurons lacking known TRP channels.
• Employed a combination of calcium imaging, electrophysiology, and RNA sequencing to characterize the function of TRPM2.
• Analyzed thermal behavior in mice with genetically deleted TRPM2.

Main Results:

• Identified a population of thermally sensitive neurons that do not express known thermosensory TRP channels.
• Demonstrated that the Transient Receptor Potential Melastatin 2 (TRPM2) ion channel mediates heat sensitivity in these neurons.
• Showed that TRPM2 is expressed in autonomic neurons and responds directly to heat.
• Observed a significant deficit in the sensation of non-noxious warm temperatures in TRPM2 knockout mice.

Conclusions:

• TRPM2 is the primary ion channel responsible for detecting non-painful warmth.
• TRPM2 initiates a 'warm' signal that influences cool-seeking behavior.
• This finding resolves a critical gap in understanding mammalian thermosensation.