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

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Kamiya K, Kodama I, Toyama J

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

Cardiovasc Res. 1991 Jun;25(6):516-22.

PubMed ID

1653644 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Aprindine	Sodium channel protein type 5 subunit alpha	Protein	Humans	Yes	Inhibitor	Details