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Altitude, temperature, circadian rhythms and exercise
Published in Adam P. Sharples, James P. Morton, Henning Wackerhage, Molecular Exercise Physiology, 2022
Henning Wackerhage, Kenneth A. Dyar, Martin Schönfelder
Temperature is sensed by TRP ion channels in the skin, viscera, spinal cord and by the brain. But where does this information go to be processed and to trigger responses to a “too hot” or “too cold” sensation? First, researchers noted that animals rapidly increased their body temperature when they damaged the base of the brain, suggesting that this houses the thermoregulatory centre (43, 44). Today we know that thermoregulatory centre is located in the hypothalamus, specifically in the preoptic area and in the anterior part.
Nonclassical Ion Channels in Depression
Published in Tian-Le Xu, Long-Jun Wu, Nonclassical Ion Channels in the Nervous System, 2021
Transient receptor potential (TRP) channels—the second largest class of ion channels in humans—act as sensors in a variety of physiological processes. The TRP channels are subdivided into seven main subfamilies based on amino acid homology: TRPC (canonical), TRPM (melastatin), TRPA (ankyrin), TRPV (vanilloid), TRPN (nomp), TRPML (mucolipin), and TRPP (polycystin)80. Several TRP channels are regulated by phosphatidylinositol 4,5-bisphosphate, while most TRP channels serve as Ca2+ import pathways. Some of these channels are constitutively open, while some are typically gated by sensing the Ca2+ concentration of intracellular Ca2+ stores81.
Functional Studies of PKD2 and PKD2L1 through Opening the Hydrophobic Activation Gate
Published in Jinghua Hu, Yong Yu, Polycystic Kidney Disease, 2019
Wang Zheng, Lingyun Wang, Jingfeng Tang, Ji-Bin Peng, Xing-Zhen Chen
Transient receptor potential (TRP) channels are a superfamily of cation channels that have emerged as cellular sensors responding to a broad range of intracellular or extracellular stimuli.1,2 The 28 TRP members in mammals have been divided into six subfamilies: TRPC (canonical), TRPM (melastatin), TRPV (vanilloid), TRPML (mucolipin), TRPA (ankyrin), TRPP (polycystin).3 During the past decades, TRP channels have been extensively studied, which greatly deepened our understanding of their channel functions and physiological functions. With the recent exciting achievements on the determination of high-resolution structures of TRPs,4 we have now gained insights into their gating and regulation mechanisms on the molecular level. However, compared with other TRP channels, our understanding of TRPP channel functions lags far behind to date, largely because of lack of reliable current readout and unknown agonist. In this chapter, we discuss the strategy and logic to constitutively open the TRPP channels through mutation to the hydrophobic activation gate.
Exposure to acute noxious heat evokes a cardiorespiratory shock response in humans
Published in International Journal of Hyperthermia, 2022
Nerijus Eimantas, Soneta Ivanove, Rima Solianik, Marius Brazaitis
The evolution of a body’s ability to detect (sense), avoid, or deal with noxious (cold or hot) temperatures is crucial for the survival of a living organism [1,2]. Over the past decades, several family members of temperature-activated, so-called thermo-transient receptor potentials (TRPs) have been put forward as potential molecular temperature sensors. They are highly expressed in skin and can be functionally activated by changes in the whole range of physiologically relevant temperatures, from painful heat through intermediate warmth to painful cold [1,3,4]. The activity of these thermo-TRP channels is regulated through their temperature-evoked currents, which increase in a steep but graded manner across their temperature activation range [1]. The higher the thermo-TRP channel current, the higher the centrally driven thermoregulatory response. The involvement of several thermo-TRP channels with overlapping expression in nociceptor neurons has been suggested to represent a powerful mechanism that ensures avoidance of noxious (cold or hot) temperatures [3,5].
TRPA1 as a therapeutic target for nociceptive pain
Published in Expert Opinion on Therapeutic Targets, 2020
Daniel Souza Monteiro de Araujo, Romina Nassini, Pierangelo Geppetti, Francesco De Logu
A variety of receptors in sensory neurons directly encode harmful stimuli that generate propagated action potentials to signal pain. These stimuli consist of physical (mechanical forces, temperature variations) and exogenous (irritants of vegetal origin such as capsaicin, menthol or isothiocyanates) and endogenous (protons, prostaglandins, kinins, and many others) chemical agents. Multi damage events may act indirectly on the nociceptors, via the release of inflammatory substances and the accumulation of inflammatory cells, which favor nociceptor sensitization to any stimulus [117]. In this context, TRP channels have been identified as potential targets and multimodal sensors of irritative and pain signals. In addition, TRP channels may cooperate to encode a specific pain signal, as in the case of noxious heat, which requires the simultaneous contribution of TRPV1, TRPM3, and TRPA1 [118]. More importantly, robust evidence indicates TRPA1 as a major player in mediating the prolonged hypersensitivity to thermal, chemical, and mechanical stimuli detected in models of nociceptive, inflammatory and neuropathic pain [11,15,119-121–122].
Mechano-gated channels in C. elegans
Published in Journal of Neurogenetics, 2020
Transient receptor potential (TRP) channels are from a family of cation channels involved in a range of sensory processes counting chemosensation, thermosensation, mechanosensation and pain sensation (Arnadottir & Chalfie, 2010; Christensen & Corey, 2007) (Figure 2). TRP channels are classified into seven subfamilies (TRPA, TRPC, TRPML, TRPM, TRPN, TRPP and TRPV), which are tetrameric cation channels that can link to other molecular complexes required in various functions (Christensen & Corey, 2007; Montell, 2005). The importance of TRP ion channels is highlighted by a plethora of diseases and channelopathies in all major organs subjected to dysfunctions or mutations (Christensen & Corey, 2007; Nilius, Voets, & Peters, 2005). Interestingly, TRP channels are also present in single-celled organisms (protozoa) like yeast but limited to only TRPL, TRPM and TRPP channels (Venkatachalam, Luo, & Montell, 2014).