Uncoupling cation effects on cardiac contractility and sarcolemmal Ca2+ binding.
Studies have been performed correlating the effects of cationic uncouplers on intact cardiac muscle and on Ca2+ bound to isolated cardiac plasma membranes. Sarcolemmal vesicles were isolated from neonatal rat hearts. Ca2+ binding experiments were performed and Scatchard plot analysis indicated two classes of Ca2+ binding sites. The ability of certain cations to displace Ca2+ bound to these vesicles was measured. The effects of these same cations on the tension developed by neonatal rat papillary muscles and on the Ca2+ content of tissue culture cells (from neonatal rat heart) were measured. The results show that a) the selectivity sequence (Y3+ greater than Nd3+ greater than La3+, Cd2+ greater than Co2+ greater than Mg2+) of sarcolemmal Ca2+ binding sites is the same as the effective uncoupling sequence; b) the amount of Ca2+ bound at these sites (approximately 700 micromol/kg wet wt) is more than adequate to support tension development; c) the dependence of sarcolemmal Ca2+ binding at low-affinity sites and tension development on [Ca2+]o is essentially the same. It is then reasonable to propose that the Ca2+ bound to these sarcolemmal sites plays an important role in controlling the amount of Ca2+ available to the myofilaments and thus myocardial contractility.
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D007811:Lanthanum / Q000494:pharmacology; D009200:Myocardial Contraction; D010210:Papillary Muscles / Q000378:metabolism*; D051381:Rats; D012508:Sarcolemma / Q000378:metabolism*
D007811:Lanthanum; D002118:Calcium