Sodium channels in rabbit cardiac Purkinje fibres

Abstract

SODIUM channels are essential for normal impulse conduction in the heart and are a major target for the therapeutic action of antiarrhythmic drugs. However, these channels have not been well studied due to the difficulty of measuring cardiac sodium currents under voltage clamp. Previous efforts have not been generally accepted because of doubts about the adequacy of voltage control^1–8. The absence of direct information on cardiac sodium channels is unfortunate as evidence exists suggesting that they differ significantly from sodium channels in other excitable membranes. First, blockade of sodium-dependent impulses in heart requires tetrodotoxin (TTX) at 10³–10⁴ times greater concentrations than in nerve or skeletal muscle⁹. Second, the effect of TTX in heart appears to be voltage-dependent¹⁰, unlike its action on sodium currents in other excitable cells^11,12. These findings raise the possibility that cardiac sodium channels may have novel structural properties. Further progress depends on the development of reliable measures of sodium current in the heart itself. We report here voltage-clamp recordings of sodium currents in rabbit Purkinje fibres satisfying a number of criteria for adequate voltage control. The experiments indicate the feasibility of characterising sodium channels in an intact mammalian cardiac preparation and open the way for the direct analysis of antiarrhythmic drug action on cardiac conducting tissue.