Dataset Information

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.

SUBMITTER: Jimenez I

PROVIDER: S-EPMC7761947 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

TRPM Channels in Human Diseases.

Jimenez Ivanka I Prado Yolanda Y Marchant Felipe F Otero Carolina C Eltit Felipe F Cabello-Verrugio Claudio C Cerda Oscar O Simon Felipe F

Cells 20201204 12

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-termin ...[more]

PMID: 33291725

Similar Datasets

Project description:BackgroundUltradian rhythms, rhythms with a period of less than 24 hours, are a widespread and fundamental aspect of life. The mechanisms underlying the control of such rhythms remain only partially understood. Defecation in C. elegans is a very tightly controlled rhythmic process. Underlying the defecation motor programme is an oscillator which functions in the intestinal cells of the animal. This mechanism includes periodic calcium release and subsequent intercellular calcium waves which in turn regulate the muscle contractions that make up the defecation motor programme. Here we investigate the role of TRPM cation channels in this process.ResultsWe use RNA interference (RNAi) to perturb TRPM channel gene expression. We show that combined knock down of two of the TRPM encoding genes, gon-2 and gtl-1, results in an increase in the variability of the cycle but no change in the mean, in normal culture conditions. By altering the mean using environmental (temperature) and genetic approaches we show that this increase in variability is separable from changes in the mean. We show that gon-2 and gtl-1 interact with components of the calcium signalling machinery (itr-1 the C. elegans inositol 1,4,5-trisphosphate receptor) and with plasma membrane ion channels (flr-1 and kqt-3) which are known to regulate the defecation oscillator. Interactions with these genes result in changes to the mean period and variability. We also show that knocking down a putative transcription factor can suppress the increased variability caused by reduction of gon-2 and gtl-1 function. We also identify a previously unrecognised tendency of the defecation cycle to compensate for cycles with aberrant length by adjusting the length of the following cycle.ConclusionThus TRPM channels regulate the variability of the defecation oscillator in C. elegans. We conclude that the mean and the variability of the defecation oscillator are separable. Our results support the notion that there is a strong underlying pacemaker which is able to function independently of the observable defecation rhythm and is not perturbed by increases in the variability of the cycle. The interaction of gon-2 and gtl-1 with other components of the oscillator shows that TRPM channels play an important role in the oscillator machinery. Such a role may be through either regulation of cation levels or membrane properties or both. Specifically our results support previous proposals that gon-2 and gtl-1 regulate IP3 signalling and that kqt-3 may act by altering calcium influx. Our results provide novel insights into the properties of the defecation oscillator and thus to our understanding of ultradian rhythms.

Project description:Lung diseases constitute a global health concern causing disability. According to WHO in 2016, respiratory diseases accounted for 24% of world population mortality, the second cause of death after cardiovascular diseases. The Kv7 channels family is a group of voltage-dependent K+ channels (Kv) encoded by KCNQ genes that are involved in various physiological functions in numerous cell types, especially, cardiac myocytes, smooth muscle cells, neurons, and epithelial cells. Kv7 channel α-subunits are regulated by KCNE1-5 ancillary β-subunits, which modulate several characteristics of Kv7 channels such as biophysical properties, cell-location, channel trafficking, and pharmacological sensitivity. Kv7 channels are mainly expressed in two large groups of lung tissues: pulmonary arteries (PAs) and bronchial tubes. In PA, Kv7 channels are expressed in pulmonary artery smooth muscle cells (PASMCs); while in the airway (trachea, bronchus, and bronchioles), Kv7 channels are expressed in airway smooth muscle cells (ASMCs), airway epithelial cells (AEPs), and vagal airway C-fibers (VACFs). The functional role of Kv7 channels may vary depending on the cell type. Several studies have demonstrated that the impairment of Kv7 channel has a strong impact on pulmonary physiology contributing to the pathophysiology of different respiratory diseases such as cystic fibrosis, asthma, chronic obstructive pulmonary disease, chronic coughing, lung cancer, and pulmonary hypertension. Kv7 channels are now recognized as playing relevant physiological roles in many tissues, which have encouraged the search for Kv7 channel modulators with potential therapeutic use in many diseases including those affecting the lung. Modulation of Kv7 channels has been proposed to provide beneficial effects in a number of lung conditions. Therefore, Kv7 channel openers/enhancers or drugs acting partly through these channels have been proposed as bronchodilators, expectorants, antitussives, chemotherapeutics and pulmonary vasodilators.

Dataset Information

TRPM Channels in Human Diseases.

Publications

TRPM Channels in Human Diseases.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets