The role of intracellular sodium activity in the anti‐arrhythmic action of local anaesthetics in sheep Purkinje fibres.

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Abstract
The effects of lidocaine were examined on the arrhythmogenic transient inward current (ITI) in voltage-clamped sheep cardiac Purkinje fibers. Tension and intracellular Na activity .**GRAPHIC**. were measured simultaneously. The addition of lidocaine (200-300 .mu.M) produced an immediate decrease of inward holding current and a gradual fall of .**GRAPHIC**. The relative magnitudes of the changes of current and .**GRAPHIC**. were consistent with the outward shift of current representing principally a reduction of inward Na current. The Na pump was inhibited by reducing the external RB concentration in a K-free solution. This produced an after-contraction and transient inward current (ITI) along with a rise of .**GRAPHIC**. The subsequent addition of lidocaine decreased the magnitude of ITI and the after contraction while decreasing .**GRAPHIC**. Tetrodotoxin (TTX) had qualitatively similar effects to lidocaine on inward holding current, .**GRAPHIC**. ITI and the after-contraction. When .**GRAPHIC**. was changed by lidocaine, TTX or small changes of external RB concentration, a hysteresis was seen in the relationship between .**GRAPHIC**. and ITI or after-contraction. The hysteresis was similar to that found between .**GRAPHIC**. and contraction. Despite this hysteresis, neither lidocaine nor TTX affected the relationship between the magnitudes of ITI and the after-contraction. The fall of .**GRAPHIC**. may be a major factor in the reduction of ITI by lidocaine. These results are discussed in relation to the anti-arrhythmic actions of lidocaine.