Cardiac fibroblasts make up a major proportion of non-excitable cells in the heart and contribute to the cardiac structural integrity and maintenance of the extracellular matrix. During myocardial injury, fibroblasts can be activated to trans-differentiate into myofibroblasts, which secrete extracellular matrix components as part of healing, but may also induce cardiac fibrosis and pathological cardiac structural and electrical remodeling. The mechanisms regulating such cellular processes still require clarification, but the identification of transient receptor potential (TRP) channels in cardiac fibroblasts could provide further insights into the fibroblast-related pathophysiology. TRP proteins belong to a diverse superfamily, with subgroups such as the canonical (TRPC), vanilloid (TRPV), melastatin (TRPM), ankyrin (TRPA), polycystin (TRPP), and mucolipin (TRPML). Several TRP proteins form non-selective channels that are permeable to cations like Na⁺ and Ca²⁺ and are activated by various chemical and physical stimuli. This review highlights the role of TRP channels in cardiac fibroblasts and the possible underlying signaling mechanisms. Changes in the expression or activity of TRPs such as TRPCs, TRPVs, TRPMs, and TRPA channels modulate cardiac fibroblasts and myofibroblasts, especially under pathological conditions. Such TRPs contribute to cardiac fibroblast proliferation and differentiation as well as to disease conditions such as cardiac fibrosis, atrial fibrillation, and fibroblast metal toxicity. Thus, TRP channels in fibroblasts represent potential drug targets in cardiac disease.

Magnesium-sensitive transient receptor potential melastatin (TRPM) ion channels, TRPM6 and TRPM7, are present in several organs, but their roles in the heart remain unclear. Therefore, here, we studied the expression patterns of TRPM6 and TRPM7 in normal and diseased myocardium. Cardiac atrial tissue and cardiomyocytes were obtained from healthy pigs and undiseased human hearts as well as from hearts of patients with ischemic heart disease (IHD) or atrial fibrillation (AF). Immunofluorescence and ELISA were used to detect TRP proteins. TRPM6 and TRPM7 immunofluorescence signals, localized at/near the cell surface or intracellularly, were detected in pig and human atrial tissues. The TRP channel modulators carvacrol (CAR, 100 µM) or 2-aminoethoxydiphenyl borate (2-APB, 500 µM) decreased the TRPM7 signal, but enhanced that of TRPM6. At a higher concentration (2 mM), 2-APB enhanced the signals of both proteins. TRPM6 and TRPM7 immunofluorescence signals and protein concentrations were increased in atrial cells and tissues from IHD or AF patients. TRPM6 and TRPM7 proteins were both detected in cardiac atrial tissue, with relatively similar subcellular localization, but distinctive drug sensitivity profiles. Their upregulated expression in IHD and AF suggests a possible role of the channels in cardiac atrial disease.

: Ethanolamine is a bioactive molecule found in several cells, including those in the central nervous system (CNS). In the brain, ethanolamine and ethanolamine-related molecules have emerged as prodrug moieties that can promote drug movement across the blood-brain barrier. This improvement in the ability to target drugs to the brain may also mean that in the process ethanolamine concentrations in the brain are increased enough for ethanolamine to exert its own neurological ac-tions. Ethanolamine and its associated products have various positive functions ranging from cell signaling to molecular storage, and alterations in their levels have been linked to neurodegenerative conditions such as Alzheimer’s disease. This mini-review focuses on the effects of ethanolamine in the CNS and highlights the possible implications of these effects for drug design.

The cardiac Mg²⁺-sensitive, TRPM6, and TRPM7-like channels remain undefined, especially with the uncertainty regarding TRPM6 expression in cardiomyocytes. Additionally, their contribution to the cardiac action potential (AP) profile is unclear. Immunofluorescence assays showed the expression of the TRPM6 and TRPM7 proteins in isolated pig atrial and ventricular cardiomyocytes, of which the expression was modulated by incubation in extracellular divalent cation-free conditions. In patch clamp studies of cells dialyzed with solutions containing zero intracellular Mg²⁺ concentration ([Mg²⁺]_i) to activate the Mg²⁺-sensitive channels, raising extracellular [Mg²⁺] ([Mg²⁺]_o) from the 0.9-mM baseline to 7.2 mM prolonged the AP duration (APD). In contrast, no such effect was observed in cells dialyzed with physiological [Mg²⁺]_i. Under voltage clamp, in cells dialyzed with zero [Mg²⁺]_i, depolarizing ramps induced an outward-rectifying current, which was suppressed by raising [Mg²⁺]_o and was absent in cells dialyzed with physiological [Mg²⁺]_i. In cells dialyzed with physiological [Mg²⁺]_i, raising [Mg²⁺]_o decreased the L-type Ca²⁺ current and the total delayed-rectifier current but had no effect on the APD. These results suggest a co-expression of the TRPM6 and TRPM7 proteins in cardiomyocytes, which are therefore the molecular candidates for the native cardiac Mg²⁺-sensitive channels, and also suggest that the cardiac Mg²⁺-sensitive current shortens the APD, with potential implications in arrhythmogenesis.

Magnesium (Mg(2+)) is effective in treating cardiovascular disorders such as arrhythmias and pre-eclampsia, but its role during myocardial infarction (MI) remains uncertain. In this study, we investigated the effects of Mg(2+)pre-treatment on isoprenaline (ISO) -induced MI in vivo. Rats divided into four groups were each pre-treated with either MgSO4 (270 mg/kg intraperitoneally) or an equivalent volume of physiological saline, prior to the ISO (67 mg/kg subcutaneously) or saline treatments. One day post-treatment, the electrocardiogram and left ventricular blood pressures were recorded. Infarcts were determined using 2,3,5-triphenyltetrazolium chloride staining, and serum markers of lipid peroxidation were measured with spectrophotometric assays. Mg(2+) pre-treatment neither altered the ISO-induced infarct size compared with ISO treatment alone (p > 0.05), nor reversed the low-voltage electrocardiogram or the prominent Q waves induced by ISO, despite a trend to decreased Q waves. Similarly, Mg(2+) did not prevent the ISO-induced decrease in peak left ventricular blood pressure or the decrease in minimal rate of pressure change. Mg(2+) did not reverse the ISO-induced gain in heart weight or loss of body weight. Neither ISO nor Mg(2+) altered the concentrations of lipid peroxidation markers 24 hours post MI induction. Although Mg(2+) had no detrimental effects on electrical or haemodynamic activity in ISO-induced MI, the lack of infarct prevention may detract from its utility in MI therapy.