Abstract
Lidocaine depresses automaticity in cardiac Purkinje fibers by decreasing the slope of slow diastolic depolarization, but the mechanisms of this effect are poorly understood. To test the proposal that the antiautomatic effect of lidocaine might be mediated by an increase in membrane potassium conductance, transmembrane voltage (Vm) was measured in Purkinje fibers perfused with sodium-deficient Tyrode containing choline as the major cation. Vm was varied by altering the external potassium concentration, [K]o, from 0.5 to 150 mM before and after lidocaine, 2.14 × 10-5 M, a concentration considered equivalent to clinical plasma antiarrhythmic levels. In Purkinje fibers, resting Vm varies linearly with [K]o plotted on a logarithmic scale from 4 to 150 mM, approximately as predicted by the Nernst equation. At [K]o of 0.5-2.7 mM, resting Vm diverges from the predicted potassium equilibrium potential (VK) resulting in an increased driving force for the outward K+ current (Vm — VK). In choline Tyrode at [K]o of 2.7 mM or less, lidocaine caused a significant increase in Vm, the change being a positive linear function of (Vm — VK) with a P < 0.01. This effect was more striking in Purkinje fibers with a Vm reduced by stretch. These findings imply that lidocaine increased membrane chord conductance for the potassium ion (gK).
Authors
Morton F. Arnsdorf, J. Thomas Bigger Jr.
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