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- W1969951876 abstract "The aim was to examine the kinetics and the degree of Na+ channel block by mexiletine under different values of external pH to produce a fractional variation of charged and uncharged forms of mexiletine.The Na+ current (INa) was recorded using the patch clamp technique of whole cell configuration in guinea pig ventricular myocytes.In the presence of 20 microM mexiletine, INa block developed with a single exponential when depolarising pulse trains of 5 ms were applied to -30 mV from a holding potential of -100 mV at a diastolic interval of 500 ms. At the 30th pulse, the degree of use dependent block of INa was 12.3(SEM 0.41)% (n = 4) of the 1st pulse. When the duration of pulses was prolonged to 200 ms, the degree of use dependent block was increased to 25.6(4.7)%, which had the block development of two exponentials with fast and slow rate constants. The slow component at the 200 ms pulses was comparable to the single exponential component at the 5 ms pulses. Drug binding to the inactivated channel was increased by external alkalinisation, which increased the uncharged form of mexiletine, whereas the block at the 5 ms pulses was not affected by the change of external pH.Uncharged mexiletine caused use dependent block with a fast rate constant having affinity for the inactivated state of the Na+ channel, while the charged form produced a slow component of the block having affinity for the activated state. Therefore the fraction of the uncharged to the charged form of mexiletine could be one of the important determinants in the development and mechanism of INa block." @default.
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- W1969951876 date "1994-07-01" @default.
- W1969951876 modified "2023-09-23" @default.
- W1969951876 title "External pH modifies sodium channel block by mexiletine in guinea pig ventricular myocytes" @default.
- W1969951876 doi "https://doi.org/10.1093/cvr/28.7.973" @default.
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