Effects of Calcium Channel Blockers on Sodium-Free Contracture in Atrial Muscle of the Rabbit

Abstract

Effects of organic and inorganic Ca-channel blockers on Na-Ca exchange system were investigated in the rabbit atrial muscle. Atrial muscle strips were perfused with Kr-free Tyrode solution in order to depress the sodium pump activity. Removal of external sodium(sodium being replaced by Tris) induced a contracture which reached a maximum after 1 min and effects of Ca-channel blockers on the magnitude of contracture were analysed. The results obtained were as follows: 1. In the concentrations of 30 pM, 100 pM and 300 ,uM Mn2 + increased the magnitude of Na-removal contracture, but decreased it in the concentration above 2 ,uM. Verapamil(IO-6 M) pretreatment did not alter the effect of Mn2+ on sodium-removal contracture. 2. La3+, as Mn2+, increased the magnitude of contracture in the concentrations of 30-300 pM, and decreased the contracture in higher concentrations(> 1 mM) more prominently than Mn2+ did. 3. 0-600 also increased the contracture in the concentrations of 5 x 10-8 M, 10-7 M and 5 x 10-7 M but had no effect in higher concentratlonsfl Orf - 10-5 M), On the other hand diltiazem had no dffect on the contracture in a wide range of concentrations (up to 10-4 M). From the above results, it is concluded that Mn2+, La3+ and 0600 in lower concentrations stimulate the Na-Ca exchange system, whereas, Mn2+, La3+ and 0-600 in higher concentrations depress the exchange system and that Na-Ca exchange might be regulated by Ca-channel blockers and this regulation is sensitive to the concentration of Ca-channel blockers.