3-methyl-phenanthrene (3-MP) disrupts the electrical and contractile activity of the heart of the polar fish, navaga cod (Eleginus nawaga)

• Published in: Chemosphere
• Main Authors: Filatova, Tatiana s., Kuzmin, Vladislav s., Dzhumaniiazova, Irina, Pustovit, Oksana b., Abramochkin, Denis v., Shiels, Holly a.
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2024
• Subjects: Arctic; cardiac toxicity; alkylated polycyclic aromatic hydrocarbons; INa; ICa; IKr; erg-channel; depolarization; repolarization; Navaga
• Online Access: https://research.manchester.ac.uk/en/publications/8af9194f-8acb-48e0-b781-bba246798ed7; https://doi.org/10.1016/j.chemosphere.2024.142089; https://pure.manchester.ac.uk/ws/files/300317328/3MP_Manuscript_noname_revision1_CLEAN_COPY.docx

Alkylated polycyclic aromatic hydrocarbons are abundant in crude oil and are enriched during petroleum refinement but knowledge of their cardiotoxicity remains limited. Polycyclic aromatic hydrocarbons (PAHs) are considered the main hazardous components in crude oil and the tricyclic PAH phenanthrene, has been singled out for its direct effects on cardiac tissue in mammals and fish. Here we test the impact of the monomethylated phenanthrene, 3-methylphenanthrene (3-MP), on the contractile and electrical function of the atria and ventricle of a polar fish, the navaga cod (Eleginus nawaga). Using patch-clamp electrophysiology in atrial and ventricular cardiomyocytes we show that 3-MP is a potent inhibitor of the delayed rectifier current IKr (EC50=0.25 μM) and prolongs ventricular action potential duration. Unlike the parent compound phenanthrene, 3-MP did not reduce the amplitude of the L-type Ca2+ current (ICa) but it accelerated current inactivation thus reducing charge transfer across the myocyte membrane and compromising pressure development of the whole heart. 3-MP was a potent inhibitor (EC50=4.7 μM) of the sodium current (INa), slowing the upstroke of the action potential in isolated cells, slowing conduction velocity across the atria measured with optical mapping, and increasing atrio-ventricular delay in a working whole heart preparation. Together, these findings reveal the strong cardiotoxic potential of this phenanthrene derivative on the fish heart. As 3-MP and other alkylated phenanthrenes comprise a large fraction of the PAHs in crude oil mixtures, these findings are worrisome for Arctic species facing increasing incidence of spills and leaks from the petroleum industry. 3-MP is also a major component of polluted air but is not routinely measured. This is also of concern if the hearts of humans and other terrestrial animals respond to this PAH in a similar manner to fish.