TRPM4 : transient receptor potential cation channel subfamily M member 4
Description
The TRPM4 (transient receptor potential cation channel subfamily M member 4) is a protein-coding gene located on chromosome 19.
The TRPM4 gene provides instructions for making a protein called transient receptor potential cation channel subfamily M member 4 (TRPM4). This protein acts as a channel, opening and closing at specific times to control the flow of positively charged atoms (cations) into and out of cells. The TRPM4 channel is embedded in the outer membrane of cells throughout the body, but it is abundant in heart (cardiac) cells and plays key roles in these cells' ability to generate and transmit electrical signals. TRPM4 channels play a major role in signaling the start of each heartbeat, coordinating the contractions of the upper and lower chambers of the heart, and maintaining a normal heart rhythm.In addition to regulating electric signaling in the heart, the TRPM4 channel is important for the normal functioning of the immune system, the nervous system, the kidneys, and the pancreas.
TRPM4 is a calcium-activated non-selective (CAN) cation channel that allows the passage of positively charged ions (Na+, K+, Cs+, and Li+) across cell membranes, leading to membrane depolarization. This depolarization plays a crucial role in various physiological processes, including:
- Cardiac Function: TRPM4 is involved in initiating heartbeats, coordinating contractions of the heart chambers, and maintaining a regular heart rhythm.
- Nervous System: TRPM4 is found in neurons of the entorhinal cortex, dorsal root, and vomeronasal systems, where it contributes to neuronal signaling.
- Immune System: TRPM4 participates in T-cell activation by modulating calcium oscillations, which are essential for the production of interleukin-2 (IL2), a key cytokine in immune responses.
- Endocrine System: TRPM4 is expressed in pancreatic beta cells and regulates insulin secretion.
- Renal System: TRPM4 is found in kidney epithelial cells and may contribute to renal function.
- Auditory System: TRPM4 is present in cochlear hair cells, suggesting a role in hearing.
Furthermore, TRPM4:
- Vascular Function: Contributes to myogenic constriction of cerebral arteries.
- Cell Proliferation: Enhances cell proliferation by upregulating the beta-catenin signaling pathway.
- Keratinocyte Differentiation: Plays a role in the differentiation of keratinocytes, which are skin cells.
- T-cell Signaling: Affects the motility and cytokine production of T-helper 1 (Th1) and T-helper 2 (Th2) cells by regulating calcium signaling and NFATC1 localization.
TRPM4 is a homotetramer, meaning it is composed of four identical protein subunits that assemble together to form the functional channel.
TRPM4 is also known as EKVP6, LTrpC4, PFHB1B, TRPM4B, hTRPM4.
Associated Diseases
- Brugada syndrome
- Progressive symmetric erythrokeratodermia
- Familial progressive cardiac conduction defect
- Progressive familial heart block, type IB
- Erythrokeratodermia veriabilis et progressiva 6
- Progressive familial heart block
