TRPM4 in cardiac electrical activity

Guinamard, Romain; Bouvagnet, Patrice; Hof, Thomas; Liu, Hui; Simard, Christophe; Sallé, Laurent

doi:10.1093/cvr/cvv213

Cited by 74 publications

(82 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…40,41 However, the membrane potential changes which last tens of seconds ( Figure 1C) evidence in favor of electroporation. It could be due to either plasma membrane electroporation or opening of nonselective channels, like TRPC3, TRPC6, or TRPM4 associated with electrophysiological effects in the myocardium.…”

Section: Discussionmentioning

confidence: 98%

Excitation of murine cardiac myocytes by nanosecond pulsed electric field

Azarov

Semenov

Casciola

et al. 2019

Cardiovasc electrophysiol

View full text Add to dashboard Cite

Introduction Opening of voltage‐gated sodium channels takes tens to hundreds of microseconds, and mechanisms of their opening by nanosecond pulsed electric field (nsPEF) stimuli remain elusive. This study was aimed at uncovering the mechanisms of how nsPEF elicits action potentials (APs) in cardiomyocytes. Methods and Results Fluorescent imaging of optical APs (FluoVolt) and Ca2+‐transients (Fluo‐4) was performed in enzymatically isolated murine ventricular cardiomyocytes stimulated by 200‐nanosecond trapezoidal pulses. nsPEF stimulation evoked tetrodotoxin‐sensitive APs accompanied or preceded by slow sustained depolarization (SSD) and, in most cells, by transient afterdepolarization waves. SSD threshold was lower than the AP threshold (1.26 ± 0.03 vs 1.34 ± 0.03 kV/cm, respectively, P < 0.001). Inhibition of l‐type calcium and sodium‐calcium exchanger currents reduced the SSD amplitude and increased the AP threshold ( P < 0.05). The threshold for Ca 2+‐transients (1.40 ± 0.04 kV/cm) was not significantly affected by a tetrodotoxin‐verapamil cocktail, suggesting the activation of a Ca 2+ entry pathway independent from the opening of Na + or Ca 2+ voltage‐gated channels. Removal of external Ca 2+ decreased the SSD amplitude ( P = 0.004) and blocked Ca 2+‐transients but not APs. The incidence of transient afterdepolarization waves was decreased by verapamil and by removal of external Ca 2+ ( P = 0.002). Conclusions The study established that nsPEF stimulation caused calcium entry into cardiac myocytes (including routes other than voltage‐gated calcium channels) and SSD. Tetrodotoxin‐sensitive APs were mediated by SSD, whose amplitude depended on the calcium entry. Plasma membrane electroporation was the most likely primary mechanism of SSD with additional contribution from l‐type calcium and sodium‐calcium exchanger currents.

show abstract

Section: Discussionmentioning

confidence: 98%

Excitation of murine cardiac myocytes by nanosecond pulsed electric field

Azarov

Semenov

Casciola

et al. 2019

Cardiovasc electrophysiol

View full text Add to dashboard Cite

show abstract

“…Excessive activation of TRPM4 is associated with various non‐malignant disorders and has been proposed to be a putative target for inhibition in numerous cardiovascular disorders and hypertension, oxidative stress‐mediated inflammatory diseases and multiple sclerosis . Trpm4 −/− mice were shown to be viable and fertile without obvious anatomical abnormalities, TRPM4‐selective inhibitor 9‐phenanthrol exerted cardioprotective effects, while the Human Protein Atlas consortium included TRPM4 as one of the 1054 potentially druggable proteins of the human proteome, indicating that TRPM4 represents a potential experimental target.…”

Section: Discussionmentioning

confidence: 99%

“…Excessive activation of TRPM4 is associated with various non-malignant disorders and has been proposed to be a putative target for inhibition in numerous cardiovascular disorders and hypertension, [45][46][47][48][49] oxidative stress-mediated inflammatory diseases 10 and multiple sclerosis. 50 Trpm4 À/À mice were shown to be viable and fertile without obvious anatomical abnormalities, 51 TRPM4-selective inhibitor 9-phenanthrol We demonstrated that TRPM4-positive DLBCL patients treated with R-CHOP exhibited significantly worse survival, consistent with its expression being associated with adverse clinical parameters.…”

Section: Discussionmentioning

confidence: 99%

TRPM4 expression is associated with activated B cell subtype and poor survival in diffuse large B cell lymphoma

et al. 2017

View full text Add to dashboard Cite

show abstract

“… a ; Kruse & Pongs, ; Guinamard et al . ). More specifically, the TRPM4 mRNA relative expression in non‐diseased human hearts indicates that it is expressed more in PF than in septum, atrium and ventricles (Kruse et al .…”

Section: Introductionmentioning

confidence: 97%

“…Indeed, the heart is known as a major TRPM4 mRNA expressing tissue (Launay et al 2002;Nilius et al 2003;Mathar et al 2014a;Kruse & Pongs, 2014;Guinamard et al 2015). More specifically, the TRPM4 mRNA relative expression in non-diseased human hearts indicates that it is expressed more in PF than in septum, atrium and ventricles (Kruse et al 2009).…”

Section: Introductionmentioning

confidence: 99%

TRPM4 non‐selective cation channels influence action potentials in rabbit Purkinje fibres

Hof

Sallé

Coulbault

et al. 2015

The Journal of Physiology

Self Cite

View full text Add to dashboard Cite

Key pointsr The transient receptor potential melastatin 4 (TRPM4) inhibitor 9-phenanthrol reduces action potential duration in rabbit Purkinje fibres but not in ventricle.r TRPM4-like single channel activity is observed in isolated rabbit Purkinje cells but not in ventricular cells.r The TRPM4-like current develops during the notch and early repolarization phases of the action potential in Purkinje cells. Abstract Transient receptor potential melastatin 4 (TRPM4) Ca2+ -activated non-selective cation channel activity has been recorded in cardiomyocytes and sinus node cells from mammals. In addition, TRPM4 gene mutations are associated with human diseases of cardiac conduction, suggesting that TRPM4 plays a role in this aspect of cardiac function. Here we evaluate the TRPM4 contribution to cardiac electrophysiology of Purkinje fibres. Ventricular strips with Purkinje fibres were isolated from rabbit hearts. Intracellular microelectrodes recorded Purkinje fibre activity and the TRPM4 inhibitor 9-phenanthrol was applied to unmask potential TRPM4 contributions to the action potential. 9-Phenanthrol reduced action potential duration measured at the point of 50 and 90% repolarization with an EC 50 of 32.8 and 36.1×10−6 mol l −1 , respectively, but did not modulate ventricular action potentials. Inside-out patch-clamp recordings were used to monitor TRPM4 activity in isolated Purkinje cells. TRPM4-like single channel activity (conductance = 23.8 pS; equal permeability for Na + and K + ; sensitivity to voltage, Ca 2+ and 9-phenanthrol) was observed in 43% of patches from Purkinje cells but not from ventricular cells (0/16). Action potential clamp experiments performed in the whole-cell configuration revealed a transient inward 9-phenanthrol-sensitive current (peak density = −0.65 ± 0.15 pA pF -1 ; n = 5) during the plateau phases of the Purkinje fibre action potential. These results show that TRPM4 influences action potential characteristics in rabbit Purkinje fibres and thus could modulate cardiac conduction and be involved in triggering arrhythmias. Abbreviations 9-phe, 9-phenanthrol; AP, action potential; APA, Action potential amplitude; APD, action potential duration; APD x , action potential duration at x % of repolarization; I Ca , voltage-gated Ca 2+ current; I K1 , inward-rectifier K + current; I Ks , slow K + current; I Na , voltage-gated Na + current; I to , transient outward current; PC, Purkinje cell; PF, Purkinje fibre; RMP, resting membrane potential; TRPM4, transient receptor potential melastatin 4; V m , transmembrane potential; V max , maximum upstroke velocity of action potential during the depolarizing phase.

show abstract

TRPM4 in cardiac electrical activity

Cited by 74 publications

References 96 publications

Excitation of murine cardiac myocytes by nanosecond pulsed electric field

Excitation of murine cardiac myocytes by nanosecond pulsed electric field

TRPM4 expression is associated with activated B cell subtype and poor survival in diffuse large B cell lymphoma

TRPM4 non‐selective cation channels influence action potentials in rabbit Purkinje fibres

Contact Info

Product

Resources

About