Potential-dependent interactions of nitrendipine and related 1,4-dihydropyridines in functional smooth muscle preparations

Interaction of nitrendipine and other Ca²⁺ channel antagonists including nifedipine, diltiazem, and D600 with intestinal smooth muscle was shown to depend on membrane potential. In the absence of extracellular Ca²⁺, guinea pig ileal longitudinal muscle does not contract and can be incubated at various K⁺ concentrations in the presence or absence of antagonist. Preincubation with elevated K⁺ prior to admission of Ca²⁺ and challenge with K⁺ to a total of 100 mM increased the activity of the antagonist. The IC₅₀ for nitrendipine incubated in the presence of 5 mM K⁺ was 5.36 x 10^-9 M and in the presence of 40 mM K⁺ was 0.53 x 10^-9 M. Other 1,4-dihydropyridines showed similar potency shifts.