Triclosan impairs excitation–contraction coupling and Ca ²⁺ dynamics in striated muscle

Abstract

Triclosan (TCS), a high-production-volume chemical used as a bactericide in personal care products, is a priority pollutant of growing concern to human and environmental health. TCS is capable of altering the activity of type 1 ryanodine receptor (RyR1), but its potential to influence physiological excitation–contraction coupling (ECC) and muscle function has not been investigated. Here, we report that TCS impairs ECC of both cardiac and skeletal muscle in vitro and in vivo. TCS acutely depresses hemodynamics and grip strength in mice at doses ≥12.5 mg/kg i.p., and a concentration ≥0.52 μM in water compromises swimming performance in larval fathead minnow. In isolated ventricular cardiomyocytes, skeletal myotubes, and adult flexor digitorum brevis fibers TCS depresses electrically evoked ECC within ∼10–20 min. In myotubes, nanomolar to low micromolar TCS initially potentiates electrically evoked Ca 2+ transients followed by complete failure of ECC, independent of Ca 2+ store depletion or block of RyR1 channels. TCS also completely blocks excitation-coupled Ca 2+ entry. Voltage clamp experiments showed that TCS partially inhibits L-type Ca 2+ currents of cardiac and skeletal muscle, and [ 3 H]PN200 binding to skeletal membranes is noncompetitively inhibited by TCS in the same concentration range that enhances [ 3 H]ryanodine binding. TCS potently impairs orthograde and retrograde signaling between L-type Ca 2+ and RyR channels in skeletal muscle, and L-type Ca 2+ entry in cardiac muscle, revealing a mechanism by which TCS weakens cardiac and skeletal muscle contractility in a manner that may negatively impact muscle health, especially in susceptible populations.

Triclosan in Toothpaste, Is There Any Real Risk for the Health?

“…El TCS, por su estructura similar a tóxicos que alteran las funciones musculares, puede inducir alteraciones en los receptores rianodina tipo 1 y tipo 2, ambos canales intercelulares mediadores de la liberación del ion Ca++ desde el retículo sarcoplásmico, siendo el Ca++ necesario para la acción del músculo esquelético y cardiaco. De manera que el TCS disminuye la capacidad y fuerza de contracción del músculo cardiaco en ratones (35). Pero contrario a lo observado en el modelo in vivo, en un estudio clínico incluyendo 438 pacientes, no se encontró ninguna relación entre el uso de PTCS durante 5 años y enfermedad cardiovascular (36).…”

Triclosan

“…In this study a mouse was given a dose that was less than 1% of what is considered to be lethal to animals. The mouse died within a minute of being given the dose of heart failure [4]. This is an important find because; disruption of Ca2+ signaling in humans can cause heart failure in humans as well.…”

“…The researches of this study altered the dosage to a lesser than the previous 1% (>12.5um) and found that the Triclosan still altered the ability for the heart to move blood and weaken the strength of the leg muscles in the mice [4].…”

“…A recent in vivo and in vitro animal study that was released in July 2012 that suggests that Triclosan affects muscle strength and blood flow in mice [4]. Triclosan might have the possibility of interfering with cardiac activity in exposed animals.…”

“…Triclosan can be absorbed through the skin into the blood stream although, skin products containing Triclosan rarely have caused irritation [4] it is listed More research is needed to assess the human health effects of exposure to Triclosan.…”