Mechanisms underlying Li+ effects on the myocardium of vertebrates

Abstract

The inotropic Li+ effects on the myocardium of frog Rana temporaria, as well as its influence on ion transport in the rat heart mitochondria (RHM), have been studied. The addition of Li+ to the normal Ringer solution (Li+-R) was found to attenuate the myocardium tension, decrease the maximal rate of tension development and its half-relaxation time. A comparison of the cardiac muscle contractile parameters in Li+-R with the effects of voltage-gated Ca2+ channel (Cav 1.2) inhibitors, verapamil and CdCl2, has shown that the negative inotropic effect of Na+ replacement by Li+ in the limited intracellular intermembrane (“fuzzy”) space is based on the block of Ca2+ influx into myoplasm via the reverse Ca2+/Na+ exchanger in the plasma membrane. This, in turn, prevents massive Ca2+-induced Ca2+ release to the myoplasm via RYR2-channels in the sarcoplasmic reticulum finally leading to the suppression of Ca2+-dependent myocardial contractions. The experiments on the Li+ effects on RHM have established that Li+ only slightly increases the passive permeability of the mitochondrial inner membrane for K+ and H+ and decreases the intensity of proton pumping from the matrix of energized mitochondria to the external medium. This may indicate no relationship between the oxidative processes in mitochondria and the decreased myocardium contractility under Na+ replacement in the medium by Li+.