[Mechanism of excitation and contraction uncoupling in frog and guinea pig myocardial fibers during block of slow sodium-calcium channels by compound D-600]

Abstract

In the experiments performed on the strips of frog's atria and ventricle it was found that rhythmic stimulation facilitated the dissociation of excitation--contraction coupling caused by D-600 compound through the block of calcium channels, i.e. D-600 prevented the increase of tension in the series of contractions or even converted positive staircase into negative one. The first contraction was affected by D-600 to a lesser degree than the subsequent ones. Guinea pig's left auriculus depressing action of D-600 was found to be strongly dependent on the frequency of stimulation. The data obtained were analysed by the model of excitation--contraction coupling. It was concluded that in amphibians as well as in mammalians tension amplitude during rhythmic activity of myocardial cells is determined mainly by Ca inflow through the excitable calcium channels. On the other hand the amplitude of the first contraction depends on the storage content determined by Ca inflow through the Ca channels open at rest. These latter channels have low sensitivity to D-600 and are better presented in atrium than in ventriculum. An increase of contraction tension observed in low sodium medium took place also under the action of D-600; in this case Ca storage was replenished by the Na-Ca exchange diffusion.