The effect of lidocaine on components of excitability in long mammalian cardiac Purkinje fibers.
In contrast to the usual microelectrode techniques employing extracellular tissue stimulation, the double microelectrode technique of intracellular constant current application and intracellular transmembrane voltage recording permits quantitative definition of the components of cardiac excitability. This technique was employed to assess the effect of lidocaine, in a concentration equivalent to clinically effective antiarrhythmic plasma levels (5 mug/ml), on membrane characteristics, cable properties, strength-duration curves and change-duration curves in long sheep Purkinje fibers in normal Tyrode's solution at [K]0 = 4.0 mM. As determined by small hyperpolarizing pulses, lidocaine increased membrane conductance (GM) where GM approximates membrane potassium conductance (GM congruent to GK congruent to gK1) and decreased both the membrane length (lambdam) and time (taum) constants. Lidocaine shifted non-normalized strength-duration curves (threshold current, Ith, vs. current duration, t) and charge-duration curves (charge threshold th, vs. t) upward without altering either the resting transmembrane voltage (Vr) or threshold voltage (Vth). Normalized strength-duration curves and charge-duration curves, however, were superimposable during the control and lidocaine periods. This is best explained by lidocaine altering passive resistance-capacitance properties by increasing membrane potassium conductance without influencing active generator properties dependent on sodium conductance. Lidocaine did not alter the passive or active membrane properties relevant to conduction velocity. By increasing membrane potassium conductance, lidocaine decreases excitability in long Purkinje fibers by increasing Ith without altering Vr or Vth, by increasing Qth; by decreasing lambdam and by rendering local circuit currents less effectual in eliciting an action potential.
D000818:Animals; D004558:Electric Stimulation; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D012756:Sheep; D013997:Time Factors
D008012:Lidocaine; D011188:Potassium