The Effects of Thallium on the Spontaneous Contraction of the Heart Muscle and the Energetic Processes in Cardiomyocyte Mitochondria

Abstract

Abstract—Thallium ions were tested for their effect on the spontaneous contraction of the frog heart muscle and rat heart mitochondria. Tl⁺ ions reduced all parameters of spontaneous contractions in heart muscle preparations when used at 1.0, 2.5, and 5 mM in Ringer’s solution. The greatest decreases were observed for the frequency of contractions, as well as the amplitudes, the rate of rise, and the rate of relaxation of twitch-type contractions. When Ca²⁺ was added to mitochondria in the presence of TlNO₃ and NaNO₃, the mitochondrial permeability transition pore (MPTP) opened in the inner mitochondrial membrane (IMM), leading to an increase in mitochondrial swelling, a reduction of the inner membrane potential, and a decrease in respiration rate in State 3 or the 2,4-dinitrophenol (DNP) uncoupling state. ADP and cyclosporine A (CsA) inhibited the Tl⁺ effects. Thus, Tl⁺-stimulated Ca²⁺ entry into cardiomyocytes may induce overloading of heart mitochondria with Ca²⁺ and Na⁺ ions and stimulate the MPTP opening in the IMM. The findings provide additional information on the mechanisms of thallium toxicity in the cardiac muscle in vivo. Tl⁺ ions are undesirable for use in myocardial tests in arrhythmia, heart failure, and especially diastolic dysfunction.