Actions of pyrethroid insecticides on sodium currents, action potentials, and contractile rhythm in isolated mammalian ventricular myocytes and perfused hearts

Pyrethroid insecticides are known to modify neuronal sodium channels, induc ing persistent, steady-state sodium current at depolarized membrane potenti als. Cardiac myocytes are also rich in sodium channels but comparatively li ttle is known about the effect of pyrethroids on the heart, or on the cardi ac sodium channel isoform. In the present study therefore, we determined th e actions of type I and type II pyrethroids against rat and guinea pig vent ricular myocytes under current and voltage clamp, and on isolated perfused rat hearts. In myocytes, tefluthrin (type I) and fenpropathrin and alpha -c ypermethrin (type II) prolonged action potentials and evoked afterdepolariz ations. The time course of sodium current (I-Na) was also prolonged by thes e compounds. Pyrethroids delayed I-Na inactivation, when measured under sel ective conditions as current sensitive to 30 muM tetrodotoxin, by increasin g the proportion of slowly inactivating current at the expense of fast inac tivating current. Further experiments, focusing on fenpropathrin, revealed that its effects on I-Na inactivation time course were dose-dependent, and the Na+ "window-current" was increased in its presence. In unstimulated, is olated hearts perfused with the same pyrethroids, the variability in contra ction amplitude increased due to variations in the intervals between heartb eats. These potentially arrhythmogenic changes are consistent with the effe cts observed at the cellular level. The type I pyrethroid tetramethrin had little effect in any of the preparations. These findings suggest that some pyrethroids possess considerable mammalian cardiac arrhythmogenic potential , the manifestation of which in vivo may depend on the route of exposure.