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• W1976969904 abstract "The mechanism of cardiac Na+ channel block by a charged class I antiarrhythmic agent, bisaramil, was studied in guinea-pig ventricular myocytes using patch-clamp techniques of whole-cell, cell-attached and inside-out configurations. Bath application of bisaramil caused the use-dependent block of whole cell Na+ current (INa) in a concentration-dependent manner and EC30 value was 2.0 microM. At 5 microM bisaramil, the degree of the use-dependent block of INa with a short (5 ms) pulse protocol (44.9 +/- 5.7% of the first pulse INa) was comparable to that with a long (200 ms) pulse protocol (42.8 +/- 5.9%). In cell-attached patches, bisaramil applied to the bath solution (external application) concentration dependently blocked macropatch Na+ currents (50.3 +/- 3.1% inhibition with 10 microM bisaramil). Internal application of bisaramil decreased the inside-out macropatch currents (82.6 +/- 1.3% inhibition with 10 microM bisaramil). Blocking effects of bisaramil applied to the bath solution were greater than those seen on the pipette application in all of the whole-cell, cell-attached and inside-out configurations. In cell-attached patches containing a single active channel, bath application of 10 microM bisaramil increased the null sweeps with a significant (P < 0.001) nonrandom clustering and decreased the total number of openings, whereas no changes in the number of openings per active sweep, unitary current amplitude, mean open time and mean closed time were observed. While the peak average current was decreased by 51.0 +/- 5.6% with 10 microM bisaramil, the number of active sweeps was decreased by 31.4 +/- 6.2%. In the presence of 10 microM bisaramil, the mean values of first latencies were significantly (P < 0.05) increased and the peak value of the first latency density function was decreased by 15.8 +/- 3.6%. From these results, we conclude that a charged tertiary amine, bisaramil interacts with cardiac Na+ channels preferentially in the activated state. Interactions with pre-open closed states might contribute to the activated channel block by the drug." @default.
• W1976969904 created "2016-06-24" @default.
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• W1976969904 date "1996-09-01" @default.
• W1976969904 modified "2023-10-17" @default.
• W1976969904 title "Blockade of cardiac Na+ channels by a charged class I antiarrhythmic agent, bisaramil: possible interaction of the drug with a pre-open closed state" @default.
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• W1976969904 doi "https://doi.org/10.1016/0014-2999(96)00461-x" @default.
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