China
Africa
Explore chapters and articles related to this topic
Nonclassical Ion Channels in Depression
Published in Tian-Le Xu, Long-Jun Wu, Nonclassical Ion Channels in the Nervous System, 2021
The pathophysiology of depression and anxiety is regulated by a variety of TRP channels. Individuals suffering from bipolar-I have shown a reduction in TRPC7 mRNA levels and an increase in basal Ca2+ levels in a patient-derived lymphoblast cell line82. The TRPC3 subtypes 3, 6, and, 7 are deficient in B lymphocytes of individuals suffering from bipolar disorder83. Moreover, single nucleotide polymorphisms (SNPs) in the TRPM2 promoter region were notably found to be associated with bipolar-II, strongly suggesting that TRPM2 polymorphisms may increase the risk of this neurological disorder84,85. Genome-wide association studies in patients with MDD have shown that TRPV4 mutations are a risk factor for depression86. In an animal model of anxiety, genetic deletion of TRPC4 or TRPC5 decreases anxious behaviors, while null mice demonstrate increased exploratory behaviors. TRPC5 knockout mice displayed deficits in their innate fear and anxiety behavior87,88. Consequently, TRPC4 and TRPC5 have been proposed as potentially useful drug targets for psychiatric disorders such as MDD, obsessive-compulsive disorder, and generalized anxiety disorder (GAD)89. TRPV4-deficient mice showed a substantial reduction in the social and depressive-associated behaviors observed in wild type90, signifying that the constitutive activation of TRPV4 by physiological brain temperature is essential for normal brain function. Moreover, disruption of TRPV4 function could lead to psychiatric symptoms.
Vascular smooth muscle: excitation, contraction and relaxation
Published in Neil Herring, David J. Paterson, Levick's Introduction to Cardiovascular Physiology, 2018
Neil Herring, David J. Paterson
ROCs are cation-conducting channels that are about three- to fivefold more permeable to Ca2+ than Na+. A lag of ~0.1-1.0 s between agonist application and channel activation indicates that a relatively slow, biochemical pathway leads to channel activation (Figure 12.6a). When an agonist binds to its G-protein-coupled receptor, for example, noradrenaline to the a1 adrenergic receptor, the activated receptor splits trimeric Gq protein into Gqa and Gqpy components, and the former activates the membrane-bound enzyme phospholipase Cp (PLCp). PLCp catalyses the breakdown of a membrane lipid, phosphatidylinositol 4,5-bisphosphate (PIP2), into cytosolic IP3 and lipophilic DAG (Figure 12.6b). DAG activates the ROCs directly, leading to extracellular Ca2+ influx and VSM contraction. Available evidence supports the involvement of short TRP channels 3, 6 and 7 (TRPC3, TRPC6 and TRPC7) as VSM ROCs, but as TRPs can form heteromultimeric channels this is almost certainly a simplified view. It also seems that IP3, like DAG, may activate TRPs directly (independently of Ca2+), certainly in the case of TRPC3. Note that the ‘phar- macomechanical’ contraction due to ROCs does not require an initial membrane depolarization, although the ROC- conducted current can cause a small, incidental depolarization (Figure 12.2c). Depolarization-independent contraction is typical of large arteries. It also appears that TRPC3 displays constitutive activity, which provides a low, background permeability in unstimulated vessels, resulting from background levels of DAG. The consequent small, inward cation current contributes to the resting potential in some arteries, and can be enhanced by vasoconstrictor agonists like noradrenaline to increase VDCC open probability.
TRPV1 Antagonist Suppresses Allergic Conjunctivitis in a Murine Model
Published in Ocular Immunology and Inflammation, 2018
Ji Young Kwon, Hyun Soo Lee, Choun-Ki Joo
In mammals, the transient receptor potential (TRP) family of ion channels located on the plasma membrane act as receptors for stimuli. The TRP family consists of six subfamilies: TRPC (canonical: TRPC1~TRPC7); TRPV (vanilloid: TRPV1~TRPV6); TRPM (melastatin: TRPM1~TRPM8); TRPP (polycystin: TRPP2, TRPP3, TRPP5); TRPML (mucolipin: TRPML1~TRPML3); and TRPA (ankyrin: TRPA1).9 Among the TRP family, the immunologic functions of TRPA1 or TRPV1 have been researched in terms of their immunologic functions in the context of allergic disease. In allergic asthma, TRPA1 or TRPV1 yielded increased Th2 cytokine levels and induced the infiltration of eosinophils into the lungs.10,11 In an allergic dermatitis model, TRPA1 or TRPV1 induced the infiltration of inflammatory cells into the skin, increased Th2 cytokine levels, and provoked itching.12–14 In allergic rhinitis, TRPA1 or TRPV1 increased Th2 cytokine levels and promoted histamine-mediated itching. The increased levels of Th2 cytokines also led to the infiltration of inflammatory cells.15,16