The polycationic compound gentamicin inhibits the calcium paradox in guinea-pig hearts

Abstract

The polycationic drug gentamicin and two calcium antagonists were studied with respect to their protecting action against the calcium paradox in perfused guinea-pig hearts. Besides the mechanograms the release of creatine kinase was recorded; in parallel experiments the Na(+)-content of the hearts was measured before and at the end of the Ca(2+)-lack period, and during re-exposure to normal [Ca2+]0. The calcium paradox was induced by perfusion, for 50 s, with Ca(2+)-free solution containing EGTA (3 x 10(-4) M). Nifedipine and verapamil in concentrations which reduced the equilibrium contractile force by 50%, only mitigated the extent of the calcium paradox, whereas gentamicin applied in a concentration also reducing the contractile amplitude by 50% was able to suppress the calcium paradox completely. The dose-response curves for nifedipine, with respect to the reduction of contractile force and contracture, were identical. In contrast, gentamicin was more effective in attenuating the contracture of the paradox than in reducing the equilibrium contractile force. The large gain of Na+ during the Ca(2+)-lack period was diminished by both nifedipine and gentamicin. The partial protection of calcium antagonists can be related to their interference with the uptake of Na+ through L-type Ca(2+)-channels during the Ca(2+)-lack period, whereas gentamicin seems to act by an additional inhibition of the Na/Ca exchange during the re-exposure to normal [Ca2+]0.