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<p>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<sub>V</sub>1.5 (I<sub>hSCN5A</sub>) and K<sub>V</sub>11.1 (I<sub>hERG</sub>) channels in the CHO-K1 heterologous expression system. 3-MP caused a dose-dependent blockade of I<sub>hERG</sub> tail current (IC<sub>50</sub> = 38.2 μM). At a concentration of 10 μM, 3-MP induced a shift in the half-activation potential (V<sub>0.5</sub>) 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<sub>0.5</sub> increased from -79.9 to -73.4 mV) and deactivation kinetics (time constant decreased from 63.5 to 46.3 msec). In contrast, I<sub>hSCN5A</sub> 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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年4月1日

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  • I. Dzhumaniiazova,
  • O. B. Pustovit,
  • D. V. Abramochkin

摘要

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 NaV1.5 (IhSCN5A) and KV11.1 (IhERG) channels in the CHO-K1 heterologous expression system. 3-MP caused a dose-dependent blockade of IhERG tail current (IC50 = 38.2 μM). At a concentration of 10 μM, 3-MP induced a shift in the half-activation potential (V0.5) 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 (V0.5 increased from -79.9 to -73.4 mV) and deactivation kinetics (time constant decreased from 63.5 to 46.3 msec). In contrast, IhSCN5A 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.