Tonic and Use‐dependent Block of Sodium Currents in Isolated Cardiac Myocytes by Bisaramil

1. The effects of bisaramil on sodium currents in rat isolated cardiac myocytes were examined by use of tight-seal, whole-cell patch clamp techniques. Bisaramil produced a concentration-dependent, readily reversible reduction in peak transient sodium current. When the sodium current was evoked at 3 s intervals the estimated ED50 for bisaramil was about 11 microM. 2. Bisaramil (16 microM) produced a shift in the inactivation curve to hyperpolarized potentials of about 10 mV, but produced no change in the voltage-dependence of activation. 3. The block of the sodium current by bisaramil showed a profound use-dependence. A concentration of 10 microM produced a considerable block of the current with repeated stimulation. The recovery from block was biphasic, showing fast and slow components which had time constants of about 40 ms and 5 s respectively. 4. Bisaramil produced little tonic block of the sodium current at concentrations of 100 microM; at 300 microM it produced tonic block of around 50%, with extreme use-dependence. 5. Bisaramil appeared not to interact primarily with the inactivated form of the channel, since lengthening the depolarizing pulses did not affect the degree of block produced.