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Voltage- and concentration-dependent effects of lidocaine on cardiac Na channel gating charge movements
1Department of Physiology and Biophysics, University of Cincinnati, College of Medicine, OH 45267-0576.
Abstract:
The effects of lidocaine, a local anesthetic and cardiac antiarrhythmic agent, were studied on cardiac nonlinear Na channel and Ca channel charge movements (gating currents) of 17-day-old embryonic chick ventricular myocytes. Gating currents were recorded following the blockade of all ionic currents and the subtraction of the linear capacity currents (-P/5). From a holding potential of -100 mV the ON charge movement (QON) displayed two kinetic components: a rapidly decaying component associated with Ca channel gating, and a slower component associated with Ca channel gating. A depolarizing prepulse to -50 mV for 125 ms reduced the fast component of QON, with little effect on the slower component. Similarly, 20 microM lidocaine also reduced the fast component of QON (Na channel charge movement) and had little effect on the slower component (Ca channel charge movement). Higher concentrations of lidocaine (125 microM) reduced both the fast and the slower components of QON. The effects of either a prepulse to -50 mV, or 20 microM lidocaine on the steady-state QON/Vm relationship were nearly identical. These results suggest that lidocaine "blocks" cardiac Na (ionic) currents by a reduction in the availability of Na channel charge movement (QON), and that this reduction is similar to that produced by voltage-dependent inactivation.
Insights
Lidocaine, an antiarrhythmic drug, reduces sodium channel charge movement in embryonic chick heart cells, similar to natural inactivation processes. This action affects cardiac Na+ currents by altering sodium channel availability.
Area of Science:
- Cardiology
- Pharmacology
- Electrophysiology
Background:
- Lidocaine is a local anesthetic and antiarrhythmic agent.
- Cardiac ion channels, particularly Na+ and Ca2+ channels, are crucial for heart rhythm.
- Understanding drug interactions with ion channels is vital for antiarrhythmic therapy.
Purpose of the Study:
- To investigate the effects of lidocaine on cardiac Na+ and Ca2+ channel gating currents (QON) in embryonic chick ventricular myocytes.
- To elucidate the mechanism by which lidocaine affects Na+ channel charge movement.
Main Methods:
- Recording of gating currents from embryonic chick ventricular myocytes after blocking ionic currents.
- Subtraction of linear capacity currents to isolate charge movement.
- Application of depolarizing prepulses and varying concentrations of lidocaine (20 microM and 125 microM).
Main Results:
- Lidocaine (20 microM) reduced the fast component of QON (Na+ channel gating) but minimally affected the slower component (Ca2+ channel gating).
- Higher lidocaine concentrations (125 microM) reduced both fast and slow components of QON.
- The effects of lidocaine on QON/Vm relationship were similar to voltage-dependent inactivation.
Conclusions:
- Lidocaine blocks cardiac Na+ currents by reducing the availability of Na+ channel charge movement.
- This reduction mechanism is comparable to voltage-dependent inactivation of Na+ channels.
- Findings provide insight into the electrophysiological effects of lidocaine on cardiac ion channels.