TRPM3 in Brain (Patho)Physiology

Abstract

Already for centuries, humankind is driven to understand the physiological and pathological mechanisms that occur in our brains. Today, we know that ion channels play an essential role in the regulation of neural processes and control many functions of the central nervous system. Ion channels present a diverse group of membrane-spanning proteins that allow ions to penetrate the insulating cell membrane upon opening of their channel pores. This regulated ion permeation results in different electrical and chemical signals that are necessary to maintain physiological excitatory and inhibitory processes in the brain. Therefore, it is no surprise that disturbances in the functions of cerebral ion channels can result in a plethora of neurological disorders, which present a tremendous health care burden for our current society. The identification of ion channel-related brain disorders also fuel the research into the roles of ion channel proteins in various brain states. In the last decade, mounting evidence has been collected that indicates a pivotal role for transient receptor potential (TRP) ion channels in the development and various physiological functions of the central nervous system. For instance, TRP channels modulate neurite growth, synaptic plasticity and integration, and are required for neuronal survival. Moreover, TRP channels are involved in numerous neurological disorders. TRPM3 belongs to the melastatin subfamily of TRP channels and represents a non-selective cation channel that can be activated by several different stimuli, including the neurosteroid pregnenolone sulfate, osmotic pressures and heat. The channel is best known as a peripheral nociceptive ion channel that participates in heat sensation. However, recent research identifies TRPM3 as an emerging new player in the brain. In this review, we summarize the available data regarding the roles of TRPM3 in the brain, and correlate these data with the neuropathological processes in which this ion channel may be involved.

Network Analysis of Symptoms Co-Occurrence in Chronic Fatigue Syndrome

“…Interestingly, neuroimaging investigations have reported abnormalities in the cerebellum of CFS patients [43,44], and CFS patients report experiencing ataxia, which is movement without coordination or loss of control of body movements [26]. Moreover, the expression of TRPM3 in the hippocampus suggests a role in memory formation and consolidation, and inflammation has been reported in the hippocampus of CFS patients [42] This current investigation is not without limitations. Indeed, there is criticism regarding the use of the Fukuda definition for the diagnosis of CFS.…”

“…Assumptions can be made concerning its function or pathophysiological role. For example, high mRNA of TRPM3 in cerebellar purkinje neurons suggests a role in coordination and movement [42]. Interestingly, neuroimaging investigations have reported abnormalities in the cerebellum of CFS patients [43,44], and CFS patients report experiencing ataxia, which is movement without coordination or loss of control of body movements [26].…”

Genetic Variants Relate to Fasting Plasma Glucose, 2-Hour Postprandial Glucose, Glycosylated Hemoglobin, and BMI in Prediabetes

“…Rs11142842, rs1891298, rs1891299, and rs11142843 are located in the region between transient receptor potential cation channel subfamily M member 3 (TRPM3) and transmembrane protein 2 (TMEM2) at chromosome 9q21.12-q21.13. TRPM3 belongs to the melastatin subfamily of TRP channels and represents a non-selective cation channel that can be activated by several different stimuli, including the neurosteroid pregnenolone sulfate, osmotic pressures, and heat (39). TRPM3 polymorphisms were reported to be associated with systemic sclerosis, aspirin-exacerbated respiratory disease (AERD), and developmental and epileptic encephalopathies (DEEs) (40)(41)(42).…”

Pruritus: A Sensory Symptom Generated in Cutaneous Immuno-Neuronal Crosstalk

“…They were recently shown as key transducers of heat-pain together with transient receptor potential melastatin 3 (TRPM3), another thermosensitive nociceptor TRP channel significantly co-expressed with TRPV1 and TRPA1. Interestingly, despite their co-expression and functional overlap in thermal nociception ( Vandewauw et al, 2018 ; Held and Tóth, 2021 ), TRPM3 is not involved in transduction of pruritus evoked by either histamine or serotonin (5-HT) and endothelin-1 (ET-1) ( Kelemen et al, 2021 ). These data suggests, that individual TRP channels, even if coexpressed by some sensory neurons, can play selective roles in certain forms of pruriception or nociception.…”