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Tonic and use‐dependent block of sodium currents in isolated cardiac myocytes by bisaramil
Author(s) -
Pugsley Michael K.,
Saint David A.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb13237.x
Subject(s) - tonic (physiology) , myocyte , sodium , sodium channel , heart block , block (permutation group theory) , medicine , chemistry , neuroscience , cardiology , biophysics , endocrinology , electrocardiography , biology , mathematics , combinatorics , organic chemistry
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 ED 50 for bisaramil was about 11 μ m . 2 Bisaramil (16 μ m ) 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 μ m 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. 5 Bisaramil produced little tonic block of the sodium current at concentrations of 100 μ m ; at 300 μ m it produced tonic block of around 50%, with extreme use‐dependence. 6 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.