Effects of D-600 on sodium current in squid axons.

The effects of the calcium antagonist D-600 (methoxyverapamil) on the excitatory inward sodium current, INa, of internally perfused squid giant axons were studied under voltage-clamp conditions. We observed little or no effect of the drug when it was added to the external solution at concentrations of 10-200 microM. Furthermore, it did not produce a frequency, or use-dependent block of INa when repetitive voltage-clamp pulses were used at rates of 2-5 Hz. However, it did produce use-dependent blockade of INa when it was placed internally at a concentration of 200 microM. These results in conjunction with other studies suggest that D-600 is a selective blocker of calcium channels in squid axons when the drug is placed in the external solution. Its effects, when placed in the internal solution, are similar to those of permanently charged local anesthetic derivatives, which also produce use-dependent block of INa.