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Review
. 2022 Jan 10;15(1):81.
doi: 10.3390/ph15010081.

Pharmacological Modulation and (Patho)Physiological Roles of TRPM4 Channel-Part 1: Modulation of TRPM4

Zsigmond Máté Kovács  1   2 , Csaba Dienes  1   2 , Tamás Hézső  1   2 , János Almássy  1 , János Magyar  1   3 , Tamás Bányász  1 , Péter P Nánási  1   4 , Balázs Horváth  1   5 , Norbert Szentandrássy  1   6
Affiliations
Review

Pharmacological Modulation and (Patho)Physiological Roles of TRPM4 Channel-Part 1: Modulation of TRPM4

Zsigmond Máté Kovács et al. Pharmaceuticals (Basel). .

Abstract

Transient receptor potential melastatin 4 is a unique member of the TRPM protein family and, similarly to TRPM5, is Ca2+-sensitive and permeable to monovalent but not divalent cations. It is widely expressed in many organs and is involved in several functions by regulating the membrane potential and Ca2+ homeostasis in both excitable and non-excitable cells. This part of the review discusses the pharmacological modulation of TRPM4 by listing, comparing, and describing both endogenous and exogenous activators and inhibitors of the ion channel. Moreover, other strategies used to study TRPM4 functions are listed and described. These strategies include siRNA-mediated silencing of TRPM4, dominant-negative TRPM4 variants, and anti-TRPM4 antibodies. TRPM4 is receiving more and more attention and is likely to be the topic of research in the future.

Keywords: 9-phenanthrol; CBA; SUR1; TRPM4; TRPM4 activator; TRPM4 inhibitor; antibody; flufenamic acid; siRNA.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structure of compounds directly activating TRPM4 or the sulfonylurea receptor 1 (SUR1)-TRPM4 co-assembled channel (diazoxide). U73122 can also activate TRPM4 in an indirect manner. All structures were created by ChemDrawPro 12.0 software.
Figure 2
Figure 2
Chemical structure of compounds activating TRPM4 indirectly. U73122 also activates TRPM4 directly. All structures were created by ChemDrawPro 12.0 software.
Figure 3
Figure 3
Chemical structure of compounds causing TRPM4 inhibition via a putative binding site. All structures were created by ChemDrawPro 12.0 software.
Figure 4
Figure 4
Chemical structure of compounds causing TRPM4 inhibition in a nonspecific manner. All structures were created by ChemDrawPro 12.0 software.
Figure 5
Figure 5
Chemical structure of compounds widely used for TRPM4 inhibition. All structures were created by ChemDrawPro 12.0 software.
Figure 6
Figure 6
Chemical structure of the newest TRPM4 inhibitors. All structures were created by ChemDrawPro 12.0 software.
See this image and copyright information in PMC

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