The role of transient receptor potential melastatin channels in compressive force‐induced contraction of primary cardiac pericytes

PMCID: PMC12172562

PMID: 40526043

DOI: 10.14814/phy2.70396

Journal: Physiological reports

Publication Date: 2025-6-17

Authors: Methner C, Cilento E, Cao Z, Iliff J, Mishra A, et al.

Key Points

• Cardiac pericytes possess mechanosensitive TRPM4 and TRPM7 channels that contribute to microvascular dysfunction during acute myocardial infarction
• TRPM4 inhibition reduced infarct size by approximately 350% in experimental models
• Targeting TRP channels may offer a novel therapeutic approach to minimize ischemic tissue damage in acute myocardial infarction

Summary

This groundbreaking study investigates the role of mechanosensitive Transient Receptor Potential (TRP) channels in cardiac pericytes during acute myocardial infarction (AMI). Researchers discovered that pericytes express TRPM4 and TRPM7 channels, which sense increased intramyocardial pressure and trigger calcium mobilization, leading to capillary constriction and potentially exacerbating ischemic damage.

Using a comprehensive approach combining in vitro and in vivo experiments, the study demonstrated that pharmacological stimulation of TRPM4 and TRPM7 channels induces calcium mobilization in cardiac pericytes. Critically, inhibiting TRPM4 in a rodent AMI model reduced infarct size by 3.5-fold, suggesting a promising therapeutic strategy for mitigating myocardial ischemic injury by preventing pericyte-mediated capillary constriction.