IADR Abstract Archives
Warm Temperature Effects on TRPM8 Knockout Mice
Objectives: Colder temperatures are detected by TRPM8, which is expressed in primary afferent neurons. While the properties of TRPM8 in colder conditions have been thoroughly studied, further comprehensive investigation into the effects of TRPM8 at warmer temperatures has not been completed. The purpose of this study is to demonstrate that TRPM8 alters afferent processes at temperatures beyond its characterized colder temperature ranges.
Methods: Two methods were used for collecting data: whole cell voltage-clamp and a temperature-based shuttle box. In the whole cell voltage-clamp, classification protocols are used for recording voltage-activated currents in trigeminal ganglia neurons. The protocols evaluated hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, voltage-gated potassium channels, and voltage-gated sodium channels. In the shuttle box assay, mice can move freely throughout nine zones with different temperatures stepped in 5°C increments. The sessions were video recorded. Time spent in each zone was evaluated by blinded investigators. The duration of the shuttle box sessions was 10 minutes.
Results: Evaluation of the shuttle box assay data indicates that male TRPM8 knockout mice spend significantly less time in areas where temperatures exceed 30°C than wild-type male mice (Holm-Šídák, p<0.001). Further, TRPM8 knockout mice from both sexes spend significantly less time in zones with recorded temperatures of 40±2.5°C than wild-type mice (Holm-Šídák, p<0.001). Electrophysiology data indicated differences in HCN conductance.
Conclusions: In this study, we have demonstrated that knocking-out the cold-sensing receptor, TRPM8, also influences temperature preference in warmer environments. Based on data from the shuttle box assay, knocking-out TRPM8 increases warmer temperature sensitivity across sexes. In addition, male TRPM8 knockout mice prefer temperatures colder than 33°C. Data for female TRPM8 knockout mice also suggest a decreased preference for warmer temperatures. These data indicate that altering TRPM8 gene expression alters sensory processes beyond the cool temperature range associated with the protein’s normal function.
Methods: Two methods were used for collecting data: whole cell voltage-clamp and a temperature-based shuttle box. In the whole cell voltage-clamp, classification protocols are used for recording voltage-activated currents in trigeminal ganglia neurons. The protocols evaluated hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, voltage-gated potassium channels, and voltage-gated sodium channels. In the shuttle box assay, mice can move freely throughout nine zones with different temperatures stepped in 5°C increments. The sessions were video recorded. Time spent in each zone was evaluated by blinded investigators. The duration of the shuttle box sessions was 10 minutes.
Results: Evaluation of the shuttle box assay data indicates that male TRPM8 knockout mice spend significantly less time in areas where temperatures exceed 30°C than wild-type male mice (Holm-Šídák, p<0.001). Further, TRPM8 knockout mice from both sexes spend significantly less time in zones with recorded temperatures of 40±2.5°C than wild-type mice (Holm-Šídák, p<0.001). Electrophysiology data indicated differences in HCN conductance.
Conclusions: In this study, we have demonstrated that knocking-out the cold-sensing receptor, TRPM8, also influences temperature preference in warmer environments. Based on data from the shuttle box assay, knocking-out TRPM8 increases warmer temperature sensitivity across sexes. In addition, male TRPM8 knockout mice prefer temperatures colder than 33°C. Data for female TRPM8 knockout mice also suggest a decreased preference for warmer temperatures. These data indicate that altering TRPM8 gene expression alters sensory processes beyond the cool temperature range associated with the protein’s normal function.