Related Experiment Video
Updated: May 5, 2026
Isolation, Culture, and Functional Characterization of Adult Mouse Cardiomyoctyes
Published on: September 25, 2013
Timing of myocardial trpm7 deletion during cardiogenesis variably disrupts adult ventricular function, conduction,
Rajan Sah1, Pietro Mesirca, Xenos Mason
1Howard Hughes Medical Institute, Department of Cardiology, Manton Center for Orphan Disease, Children's Hospital Boston, 320 Longwood Ave, Enders 1309, Boston, MA 02115, USA.
Background:
Transient receptor potential (TRP) channels are a superfamily of broadly expressed ion channels with diverse physiological roles. TRPC1, TRPC3, and TRPC6 are believed to contribute to cardiac hypertrophy in mouse models. Human mutations in TRPM4 have been linked to progressive familial heart block. TRPM7 is a divalent-permeant channel and kinase of unknown function, recently implicated in the pathogenesis of atrial fibrillation; however, its function in ventricular myocardium remains unexplored.
Methods And Results:
We generated multiple cardiac-targeted knockout mice to test the hypothesis that TRPM7 is required for normal ventricular function. Early cardiac Trpm7 deletion (before embryonic day 9; TnT/Isl1-Cre) results in congestive heart failure and death by embryonic day 11.5 as a result of hypoproliferation of the compact myocardium. Remarkably, Trpm7 deletion late in cardiogenesis (about embryonic day 13; αMHC-Cre) produces viable mice with normal adult ventricular size, function, and myocardial transcriptional profile. Trpm7 deletion at an intermediate time point results in 50% of mice developing cardiomyopathy associated with heart block, impaired repolarization, and ventricular arrhythmias. Microarray analysis reveals elevations in transcripts of hypertrophy/remodeling genes and reductions in genes important for suppressing hypertrophy (Hdac9) and for ventricular repolarization (Kcnd2) and conduction (Hcn4). These transcriptional changes are accompanied by action potential prolongation and reductions in transient outward current (Ito; Kcnd2). Similarly, the pacemaker current (If; Hcn4) is suppressed in atrioventricular nodal cells, accounting for the observed heart block.
Conclusions:
Trpm7 is dispensable in adult ventricular myocardium under basal conditions but is critical for myocardial proliferation during early cardiogenesis. Loss of Trpm7 at an intermediate developmental time point alters the myocardial transcriptional profile in adulthood, impairing ventricular function, conduction, and repolarization.
Insights
Transient receptor potential melastatin 7 (TRPM7) is crucial for early heart development. Loss of TRPM7 during development leads to heart failure, while adult hearts tolerate its absence.
Area of Science:
- Cardiovascular Biology
- Ion Channel Physiology
- Developmental Biology
Background:
- Transient receptor potential (TRP) channels are vital ion channels with diverse physiological roles.
- TRPM7, a divalent-permeant channel and kinase, is implicated in atrial fibrillation, but its role in ventricular myocardium is unknown.
- Previous studies link other TRP channels (TRPC1, TRPC3, TRPC6) to cardiac hypertrophy and TRPM4 mutations to heart block.
Purpose of the Study:
- To investigate the role of TRPM7 in ventricular myocardium function and development.
- To determine if TRPM7 is essential for normal cardiac development and adult ventricular function.
- To explore the consequences of TRPM7 deletion at different developmental stages.
Main Methods:
- Generation of cardiac-targeted knockout mice with TRPM7 deletion at various developmental time points (early, intermediate, late).
- Assessment of cardiac function, morphology, and survival in knockout mice.
- Analysis of myocardial transcriptional profiles using microarray.
- Electrophysiological studies to evaluate action potentials and ionic currents.
Main Results:
- Early deletion of TRPM7 (before embryonic day 9) caused embryonic lethality due to hypoproliferation of compact myocardium.
- Late deletion of TRPM7 (around embryonic day 13) resulted in viable adult mice with normal ventricular function.
- Intermediate deletion led to cardiomyopathy, heart block, and arrhythmias in 50% of mice, associated with altered gene expression (e.g., reduced Hdac9, Kcnd2, Hcn4).
- Electrophysiological changes included action potential prolongation and reduced transient outward current (Ito) and pacemaker current (If).
Conclusions:
- TRPM7 is critical for myocardial proliferation during early cardiogenesis.
- TRPM7 is dispensable in adult ventricular myocardium under basal conditions.
- Loss of TRPM7 during intermediate development alters adult myocardial transcriptional profiles, impairing ventricular function, conduction, and repolarization.
More Related Videos
03:45Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
09:36Dual-Dye Optical Mapping of Hearts from RyR2R2474S Knock-In Mice of Catecholaminergic Polymorphic Ventricular Tachycardia
Published on: December 22, 2023
Related Concept Videos
01:28Mechanism of Cardiac Arrhythmias
01:30Cardiac Action Potential
The cardiac action potential process involves a series of phases characterized by the movement of ions across the cardiac cell membranes, leading to the depolarization and repolarization of the cardiac myocytes.
Ionic Basis of Cardiac Action Potentials
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy