Sheng-Che Lin, Yang-Kao Wang, Sheng-Nan Wu, Edmund Cheung So
The effects of deltamethrin (DLT), alone or in combination with dapagliflozin (Dapa) or KB-R7943, on INa were investigated in HL-1 cardiomyocyte and U2OS osteosarcoma cells. DLT increased both transient INa (INa(T)) and tail INa in HL-1 cells. DLT exposure enhanced the persistent INa (INa(P)) in simulated mouse or guinea-pig ventricular action potentials (APs) while co-treatment of Dapa or KB-R7943 attenuated it. DLT altered the repolarization phase of simulated mouse ventricular APs, reversing the negative-slope conductance of INa(P) to positive and was subsequently ameliorated by Dapa. In guinea-pig ventricular Aps, DLT increases INa(P) while co-treatment with KB-R7943 attenuated it. U2OS cells displayed measurable INa to brief depolarizing pulses, and was significantly enhanced by DLT. Application of either Dapa or KB-R7943 effectively reversed this DLT-induced increase in INa amplitude. Our findings show that DLT exerts a stimulatory effect on INa in both cardiac and osteoblastic cells, while Dapa and KB-R7943 counteracted it.