3-iodothyronamine (T(1)AM) is a novel endogenous relative of thyroid hormone, 
able to interact with trace amine-associated receptors, a class of plasma 
membrane G protein-coupled receptors, and to produce a negative inotropic and 
chronotropic effect. In the isolated rat heart 20-25 microM T(1)AM decreased 
cardiac contractility, but oxygen consumption and glucose uptake were either 
unchanged or disproportionately high when compared to mechanical work. In adult 
rat cardiomyocytes acute exposure to 20 microM T(1)AM decreased the amplitude 
and duration of the calcium transient. In patch clamped cardiomyocytes 
sarcolemmal calcium current density was unchanged while current facilitation by 
membrane depolarization was abolished consistent with reduced sarcoplasmic 
reticulum (SR) calcium release. In addition, T(1)AM decreased transient outward 
current (I(to)) and I(K1) background current. SR studies involving 20 microM 
T(1)AM revealed a significant decrease in ryanodine binding due to reduced 
B(max), no significant change in the rate constant of calcium-induced calcium 
release, a significant increase in calcium leak measured under conditions 
promoting channel closure, and no effect on oxalate-supported calcium uptake. 
Based on these observations we conclude T(1)AM affects calcium and potassium 
homeostasis and suggest its negative inotropic action is due to a diminished 
pool of SR calcium as a result of increased diastolic leak through the ryanodine 
receptor, while increased action potential duration is accounted for by 
inhibition of I(to) and I(K1) currents.