TRPM Channels in Human Diseases

Abstract

The transient receptor potential melastatin (TRPM) subfamily belongs to the TRP cation channels family. Since the first cloning of TRPM1 in 1989, tremendous progress has been made in identifying novel members of the TRPM subfamily and their functions. The TRPM subfamily is composed of eight members consisting of four six-transmembrane domain subunits, resulting in homomeric or heteromeric channels. From a structural point of view, based on the homology sequence of the coiled-coil in the C-terminus, the eight TRPM members are clustered into four groups: TRPM1/M3, M2/M8, M4/M5 and M6/M7. TRPM subfamily members have been involved in several physiological functions. However, they are also linked to diverse pathophysiological human processes. Alterations in the expression and function of TRPM subfamily ion channels might generate several human diseases including cardiovascular and neurodegenerative alterations, organ dysfunction, cancer and many other channelopathies. These effects position them as remarkable putative targets for novel diagnostic strategies, drug design and therapeutic approaches. Here, we review the current knowledge about the main characteristics of all members of the TRPM family, focusing on their actions in human diseases.

The Antibody Receptor Fc Gamma Receptor IIIb Induces Calcium Entry via Transient Receptor Potential Melastatin 2 in Human Neutrophils

“…TRP channels are expressed in many cell types and participate in multitude of physiological and pathological processes, such as cell proliferation, differentiation, and death ( 21 ). They are particularly important as biosensors of environmental and cellular stimuli including heat, mechanical force (pressure), oxidative (redox) status, and pH ( 21 , 22 , 86 ). The family of TRP channels is divided in six subfamilies: the ankyrin (TRPA), the canonical (TRPC), the melastatin (TRPM), the mucolipin (TRPML), the polycystin (TRPP) and the vanilloid (TRPV) subfamilies.…”

“…Transient Receptor Potential Melastatin 2 (TRPM2), a nonselective Ca 2+ -permeable membrane cation channel, is highly expressed in myeloid cells ( 19 , 20 ). This receptor is a member of the TRP family of cation-selective channels that are weakly voltage-sensitive and diversely opened by temperature, mechanical force, pH, and oxidative stress ( 21 , 22 ). TRPM2 can be opened through directly binding with intracellular adenosine diphosphate ribose (ADPR) ( 23 ) and can also be indirectly activated under conditions of oxidative stress ( 24 , 25 ), acidification ( 26 ), and elevated intracellular Ca 2+ ( 27 ).…”

TRP Channels as Sensors of Aldehyde and Oxidative Stress

“…TRPV channels have also been described to be involved in bladder disease, cancer, and Alzheimer's disease [9]; diabetes mellitus [60]; in diseases of the cardiovascular, digestive, and respiratory systems [54,107]; as well as in inflammatory processes and immune response regulation [99]. The TRPM cation channels are involved in Alzheimer's disease, allergy, and stroke, as well as in diabetes mellitus and bladder, breast, and lung cancer [9,108,109]. Mutations in TRPM3 are related to various forms of glaucoma and cataracts [108,110,111], whereas TRPM2 modulates renal fibrosis and inflammatory responses [112][113][114][115].…”

Potential Implications of Mammalian Transient Receptor Potential Melastatin 7 in the Pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Review

“…Moreover, knockdown of TRPM7 in primary cortical neurons also coincided with downregulation of TRPM2, suggesting that TRPM2 and TRPM7 monomers may be co-expressed in the central nervous system (CNS) [45]. Functionally, both TRPM2 and TRPM7 activity are modulated by reactive oxygen species (ROS), further suggesting a crosstalk between these two proteins [37].…”

“…A growing body of research identifies a role for TRPM7 in metabolic [15][16][17][18][19], immunological [20][21][22][23], neurological [24][25][26][27][28][29][30][31], and cardiovascular [32][33][34] function. Similarly, dysregulation of TRPM7 channel-kinase activity is increasingly implicated in diseases affecting these systems [35][36][37]. In this review, the relevant biochemical properties of TRPM7 for metabolic, immunological, neurological, and cardiovascular physiology and pathophysiology will be outlined.…”