Effects of cadmium on the slow inward current of frog heart muscle in relation to a lowering of pH in external solution.

1. The effect of cadmium (Cd) on the slow inward current (Isi) of frog atrial fibres was studied by the double sucrose gap technique. 2. Cd (5 microM) depressed Isi in a voltage-dependent manner without alteration of the apparent reversal potential for Isi. 3. Dose-response curves indicated an apparent dissociation constant for the Cd blocking effect of 4.5 microM at 0 mV, with a one to one relationship between Cd and the slow channel. 4. Increasing the external concentration of Ca ions ([Ca]0) in the tetrodotoxin (TTX)-containing Ringer solution antagonized the block of Isi by Cd. Double reciprocal plots for Isi versus [Ca]0 drawn in the presence or in the absence of Cd intersected at the ordinate, indicating that Cd competes with Ca for a common binding site. 5. Lowering the external pH from 7.3 to 6.3 depressed Isi. The block caused by H was voltage-dependent. Double reciprocal plots for Isi versus [Ca]0 drawn at pH 7.3 and 6.3 intersected at the abscissa, and indicated that H and Ca did not compete for a common site. 6. Lowering the external pH did not change the ability of Cd to inhibit Isi. 7. The data suggested the existence of two different sites within the slow channel in frog atrial fibres, one of them being H-sensitive and the other cadmium-sensitive.