The Effects of 3-Methylphenanthrene on Ion Currents Mediated by KV11.1 and NaV1.5 Channels in the Heterologous Expression System CHO-K1.

Abstract

Polycyclic aromatic hydrocarbons are widespread environmental pollutants that can accumulate in tissues and affect numerous physiological functions. Using the patch-clamp technique, we characterized the effects of an aromatic hydrocarbon 3-methylphenanthrene (3-MP) on currents mediated by the α-subunits of Na_V1.5 (I_hSCN5A) and K_V11.1 (I_hERG) channels in the CHO-K1 heterologous expression system. 3-MP caused a dose-dependent blockade of I_hERG tail current (IC₅₀ = 38.2 μM). At a concentration of 10 μM, 3-MP induced a shift in the half-activation potential (V_0.5) from -46.5 to -51.3 mV and reduced the time required for 50% of channels to become available from 120.9 to 99.6 msec. Significant changes were observed in inactivation parameters (V_0.5 increased from -79.9 to -73.4 mV) and deactivation kinetics (time constant decreased from 63.5 to 46.3 msec). In contrast, I_hSCN5A remained tolerant to the effects of 3-MP. Therefore, it can be assumed that 3-MP can lead to lengthening of the action potential in human working cardiomyocytes, without significantly altering its amplitude or the rate of its propagation.