Upregulation of the rat cardiac sodium channel by in vivo treatment with a class I antiarrhythmic drug.
Class I antiarrhythmic drugs inhibit the sodium channel by binding to a drug receptor associated with the channel. In this report we show that in vivo administration of the class I antiarrhythmic drug mexiletine to rats induces sodium channel upregulation in isolated cardiac myocytes. The number of sodium channels was assessed with a radioligand assay using the sodium channel-specific toxin [3H]batrachotoxinin benzoate ([3H]BTXB). The administration of mexiletine to rats induced a dose-dependent increase in [3H]BTXB total specific binding (Bmax) on isolated cardiac myocytes. Sodium channel numbers were 15 +/- 5, 29 +/- 9, and 54 +/- 4 fmol/10(5) cells after 3 d treatment with 0, 50 mg/kg per d, and 150 mg/kg per d mexiletine (P less than 0.001, analysis of variance). Sodium channel number increased monoexponentially to a steady-state value within 3 d with a half-time of increase of 1.0 d. After cessation of treatment with mexiletine the number of sodium channels returned to normal within 12 d. Finally, treatment with mexiletine altered only sodium channel number; the Kd for [3H]BTXB and the IC50 for mexiletine were not different for myocytes prepared from control and mexiletine-treated rats.[1]References
- Upregulation of the rat cardiac sodium channel by in vivo treatment with a class I antiarrhythmic drug. Taouis, M., Sheldon, R.S., Duff, H.J. J. Clin. Invest. (1991) [Pubmed]
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