Quantitative differences between the inhibitory action of verapamil and Ni ions on the slow response action potential in mammalian ventricular myocardium

Abstract

Some organic compounds and a number of bivalent cations have been found capable of blocking the slow inward current ( I si) that is mainly carried by Ca in mammalian ventricular myocardium. With respect to verapamil and Ni ions, it has been shown that the mode of action of both inhibitory agents is, despite their different chemical structure, quite similar and predominantly arises from a decrease of maximum conductance of the slow channel system, g si [2, 3]. Moreover, at a given verapamil or Ni concentration, the degree of inhibition of I si depends crucially on the external Ca concentration. This supports the hypothesis that the decline of g si results from a competitive interaction of these inhibitors with Ca at certain groups of the slow channel, thereby making these (anionic) groups unable to allow Ca inward movements through the slow channel during excitation. In an attempt to further characterize the reaction of verapamil and Ni ions with their receptor molecules of the cardiac membrane, a quantitative analysis of the verapamil and Ni-induced inhibition of the I si-mediated slow response action potential was performed in isolated papillary muscles of guinea pigs.