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Lidocaine blocks Na, Ca and K currents of chick ventricular myocytes
1Department of Physiology and Biophysics, Wright State University, Dayton, Ohio 45267.
Abstract:
In addition to the well-known reduction in the maximal rate of rise the antiarrhythmic agent, lidocaine, also produces a shortening in the duration of the normal ventricular action potential. The voltage-dependent currents carried by Na, Ca and K ions were examined in the absence and presence of lidocaine, in order to identify the ionic mechanism(s) underlying the action potential shortening. Whole-cell and single channel currents were studied by the patch clamp method using single ventricular myocytes from embryonic chick hearts. Exposure to lidocaine (10 to 1000 microM) produced a decrease in the magnitude of the small-magnitude, slowly-inactivating component of the Na current, and a decrease in the magnitude of the Ca current; these results provide a mechanism for the action potential shortening and suggest possible explanations for the antiarrhythmic action of this therapeutic agent. A decrease in the magnitude of the inwardly-rectifying K+ current was also found, which was attributable to a reduction in the probability of opening of single K+ channels.
Insights
Lidocaine shortens ventricular action potential duration by reducing sodium (Na), calcium (Ca), and potassium (K) ion currents. These ionic changes in cardiac myocytes explain lidocaine's antiarrhythmic effects.
Area of Science:
- Cardiology
- Pharmacology
- Electrophysiology
Background:
- Lidocaine is an antiarrhythmic drug known to reduce the maximal rate of rise in cardiac action potentials.
- The effect of lidocaine on the duration of the ventricular action potential is less understood.
- Investigating the ionic mechanisms is crucial for understanding lidocaine's therapeutic action.
Purpose of the Study:
- To identify the specific ionic currents affected by lidocaine.
- To elucidate the mechanism behind lidocaine-induced ventricular action potential shortening.
- To provide a basis for the antiarrhythmic properties of lidocaine.
Main Methods:
- Whole-cell and single-channel patch clamp techniques were employed.
- Experiments were conducted on single ventricular myocytes isolated from embryonic chick hearts.
- Voltage-dependent ionic currents (Na, Ca, K) were analyzed in the presence and absence of lidocaine.
Main Results:
- Lidocaine (10-1000 microM) decreased the magnitude of the slowly inactivating Na+ current component.
- Lidocaine reduced the magnitude of the Ca2+ current.
- A decrease in the inwardly-rectifying K+ current was observed, linked to reduced single K+ channel opening probability.
Conclusions:
- Lidocaine shortens ventricular action potential duration by inhibiting specific Na+, Ca2+, and K+ currents.
- These ionic current modifications offer a mechanistic explanation for lidocaine's antiarrhythmic efficacy.
- The findings contribute to understanding the electrophysiological basis of lidocaine's therapeutic effects.