THE EFFECT OF VERAPAMIL ON THE Ca2+‐TRANSPORTING AND Ca2+‐ATPase ACTIVITY OF ISOLATED CARDIAC SARCOLEMMAL PREPARATIONS

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Abstract
1 The effect of (±)-, (+)- and (-)-verapamil on the Ca2+-binding, Ca2+-transporting activity, and Ca2+-dependent adenosine triphosphatase (ATPase) activity of isolated cardiac sarcolemmal preparations was studied. Enzymatic treatment was used to establish the nature of the sites facilitating [14C]-(±)-verapamil binding. 2 (±)-Verapamil 1 μm inhibited the passive binding of 45Ca2+. The (+)- and (-)-isomers were equiactive. 3 (±)-Verapamil 1 μm inhibited the ATP-dependent transport of 45Ca2+ and the associated activation of the Ca2+-sensitive ATPase. The activity resided in the (-)-isomer. 4 Lineweaver-Burk plots for the initial rates of ATP-dependent transport showed that the inhibition induced by the (-)-isomer was accompanied by a reduced Km and Vmax. 5 Enzymatic removal of N-acetyl neuraminic acid and galactose residues increased [14C]-(±)-verapamil binding; removal of N-acetylglucosamine and treatment with phospholipase C and trypsin decreased the binding. 6 These results have been interpreted to mean that (-)-verapamil interferes with the ATP-dependent Ca2+-transporting properties of the sarcolemma, and that this effect is accompanied by an altered activity of the intrinsic Ca2+-sensitive ATPase. N-acetylneuraminic acid and galactose residues do not provide binding sites for verapamil at the cell surface.