Effects of diltiazem and verapamil on responses to acetylcholine

1. The calcium channel antagonists diltiazem and verapamil were found to alter the average lifetime of ion channels activated by acetylcholine (ACh). 2. Average channel lifetime was determined from the decay phase of miniature endplate currents at the neuromuscular junction of mouse hemidiaphragms and from direct recording of single channel currents activated by ACh from BC3H1 mouse tumour cells in culture. 3. Both diltiazem and verapamil reduced average channel lifetime in a dose-dependent manner. For each drug, concentrations as high as 20 microM-100 microM were required to decrease channel lifetime by 50%. 4. Single channel recording experiments also showed that both diltiazem and verapamil greatly decreased the frequency of opening events at concentrations as low as 2 microM to 5 microM. This finding is consistent with an enhancement of receptor desensitization.