scholarly journals Role of TRPM8 in Switching Between Fever and Hypothermia in Adult Mice During Endotoxin-Induced Inflammation

2020 ◽  
Author(s):  
Chinatsu Shiraki ◽  
Ririka Horikawa ◽  
Momoka Fujimoto ◽  
Kaho Okamoto ◽  
Erkin Kurganov ◽  
...  
Keyword(s):  
Low Dose ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
High Dose ◽  
Wild Type ◽  
Adult Mice ◽  
Severe Hypothermia ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor

Abstract Transient receptor potential melastatin 8 (TRPM8) functions in the sensing of noxious and innocuous colds; however, its significance in pathogen-induced thermoregulation and inflammation remains unclear. In the present study, we investigated the role of TRPM8 in the regulation of endotoxin-induced body temperature control and inflammation. The peripheral administration of low-dose LPS or zymosan generated fever in wild-type (WT) mice and hypothermia in TRPM8 knockout (KO) animals. TRPM8 KO mice exhibited severe hypothermia and sickness responses following the peripheral administration of high-dose LPS. An intracerebroventricular injection of LPS and interleukin-1ß (Il-1ß) elicited hypothermia in TRPM8 KO mice, in contrast to fever in WT animals, whereas that of prostaglandin E2 induced normal fever. Fos immunohistochemistry showed the stronger activation of hypothalamic thermoregulation-associated nuclei following the peripheral administration of low-dose LPS. Therefore, TRPM8 is necessary for switching between fever and hypothermia during endotoxin-induced inflammation.

scholarly journals Novel regulatory mechanism in human urinary bladder: central role of transient receptor potential melastatin 4 channels in detrusor smooth muscle function

2016 ◽  
Vol 310 (7) ◽  
pp. C600-C611 ◽  
Author(s):  
Kiril L. Hristov ◽  
Amy C. Smith ◽  
Shankar P. Parajuli ◽  
John Malysz ◽  
Eric S. Rovner ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Transient Receptor Potential ◽  
Single Cells ◽  
Receptor Potential ◽  
Detrusor Smooth Muscle ◽  
Rt Pcr ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor ◽  
Trpm4 Channel

Transient receptor potential melastatin 4 (TRPM4) channels are Ca2+-activated nonselective cation channels that have been recently identified as regulators of detrusor smooth muscle (DSM) function in rodents. However, their expression and function in human DSM remain unexplored. We provide insights into the functional role of TRPM4 channels in human DSM under physiological conditions. We used a multidisciplinary experimental approach, including RT-PCR, Western blotting, immunohistochemistry and immunocytochemistry, patch-clamp electrophysiology, and functional studies of DSM contractility. DSM samples were obtained from patients without preoperative overactive bladder symptoms. RT-PCR detected mRNA transcripts for TRPM4 channels in human DSM whole tissue and freshly isolated single cells. Western blotting and immunohistochemistry with confocal microscopy revealed TRPM4 protein expression in human DSM. Immunocytochemistry further detected TRPM4 protein expression in DSM single cells. Patch-clamp experiments showed that 9-phenanthrol, a selective TRPM4 channel inhibitor, significantly decreased the transient inward cation currents and voltage step-induced whole cell currents in freshly isolated human DSM cells. In current-clamp mode, 9-phenanthrol hyperpolarized the human DSM cell membrane potential. Furthermore, 9-phenanthrol attenuated the spontaneous phasic, carbachol-induced and nerve-evoked contractions in human DSM isolated strips. Significant species-related differences in TRPM4 channel activity between human, rat, and guinea pig DSM were revealed, suggesting a more prominent physiological role for the TRPM4 channel in the regulation of DSM function in humans than in rodents. In conclusion, TRPM4 channels regulate human DSM excitability and contractility and are critical determinants of human urinary bladder function. Thus, TRPM4 channels could represent promising novel targets for the pharmacological or genetic control of overactive bladder.

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