A combination of inactivated sodium channel blockers causes competitive interaction on dV/dtmax of single ventricular myocytes.

STUDY OBJECTIVE

The aim was to study an interaction between class I antiarrhythmic drugs on the cardiac sodium channels.

DESIGN

The single pipette, whole cell clamp method was employed to control and record membrane potential. The maximum upstroke velocity (dV/dtmax) was measured as an index of sodium channel availability during treatment of the preparations with aprindine (5 microM) in combination with mexiletine (40 microM), and lignocaine (40 microM).

EXPERIMENTAL MATERIAL

Single ventricular myocytes (n = 6-8 per experiment) isolated from guinea pig hearts were used.

MEASUREMENTS AND MAIN RESULTS

Trains of depolarisation to 0 mV (0.2-2.0 Hz) were applied from the resting membrane potential (-85 mV) following a long quiescent period to evaluate "tonic" and "use dependent" decrease (block) of dV/dtmax. Additional application of mexiletine or lignocaine to aprindine resulted in an increase of tonic block and a decrease of use dependent block. Because of such counteracting action, the steady state dV/dtmax during the train of depolarisation was unaffected for mexiletine, and even increased for lignocaine. Dual exponential components of dV/dtmax recovery following a 1 s conditioning depolarisation after admixture of mexiletine or lignocaine to aprindine suggest their competitive interaction on cardiac sodium channels.

CONCLUSION

A combination of class I antiarrhythmic drugs having high affinity for the inactivated state of sodium channels may cause a reductive effect on dV/dtmax through competitive displacement from common receptors.