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The role of intracellular sodium activity in the anti‐arrhythmic action of local anaesthetics in sheep Purkinje fibres.
Author(s) -
Eisner D A,
Lederer W J,
Sheu S S
Publication year - 1983
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1983.sp014761
Subject(s) - lidocaine , contraction (grammar) , tetrodotoxin , chemistry , purkinje fibers , medicine , anesthesia , endocrinology , electrophysiology
The effects of lidocaine have been examined on the arrhythmogenic transient inward current (ITI) in voltage‐clamped sheep cardiac Purkinje fibres. Tension and intracellular Na activity (aiNa) were measured simultaneously. The addition of lidocaine (200‐300 microM) produced an immediate decrease of inward holding current and a gradual fall of aiNa. The relative magnitudes of the changes of current and aiNa were shown to be 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 aiNa. The subsequent addition of lidocaine decreased the magnitude of ITI and the after‐contraction while decreasing aiNa. Tetrodotoxin (TTX) had qualitatively similar effects to lidocaine on inward holding current, aiNa, ITI and the after‐contraction. When aiNa was changed by (i) lidocaine, (ii) TTX or (iii) small changes of external Rb concentration, a hysteresis was seen in the relationship between aiNa and ITI or after‐contraction. The hysteresis was similar to that previously found between aiNa and contraction (Eisner, Lederer & Vaughan‐Jones, 1981). Despite this hysteresis, neither lidocaine nor TTX affected the relationship between magnitudes of ITI and the after‐contraction. It is suggested that the fall of aiNa is a major factor in the reduction of ITI by lidocaine. These results are discussed in relation to the anti‐arrhythmic actions of lidocaine.