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.
Pugsley
M K
MK
Department of Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Saint
D A
DA
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002722:Chlorobenzenes; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*
D000889:Anti-Arrhythmia Agents; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002722:Chlorobenzenes; D015222:Sodium Channels; C045644:bisaramil