Molecular Prerequisites for Diminished Cold Sensitivity in Ground Squirrels and Hamsters

Area of Science:

• Molecular biology
• Mammalian physiology
• Neuroscience

Background:

• Hibernating mammals, such as thirteen-lined ground squirrels and Syrian hamsters, possess remarkable cold tolerance.
• This cold tolerance extends beyond hibernation, being present even in their active states.

Purpose of the Study:

• To investigate the molecular mechanisms underlying the cold tolerance observed in hibernating mammals.
• To identify specific adaptations in sensory neurons and ion channels responsible for reduced cold sensitivity.

Main Methods:

• Utilized imaging and electrophysiology techniques on squirrel somatosensory neurons.
• Characterized the function of TRPM8 channels in hibernators (ground squirrels, Syrian hamsters) and compared them to a non-hibernator (rat).
• Performed domain swapping and site-directed mutagenesis experiments on TRPM8 channels.

Main Results:

• Squirrel and hamster TRPM8 channels show reduced cold activation compared to rat TRPM8.
• Transferring the transmembrane domain from rat TRPM8 restored cold sensitivity to hibernator channels.
• Specific mutations in the transmembrane domain of squirrel TRPM8 were sufficient to reintroduce cold sensitivity.

Conclusions:

• Ground squirrels and Syrian hamsters exhibit inherent cold tolerance due to modifications in their TRPM8 channels.
• Alterations within the transmembrane domain of TRPM8 are key molecular adaptations contributing to cold tolerance in mammalian hibernators.