Transcripts of Kv7.1 and MinK channels and slow delayed rectifier K+ current (IKs) are expressed in zebrafish (Danio rerio) heart

Abstract

Zebrafish are increasingly used as a model for human cardiac electrophysiology, arrhythmias, and drug screening. However, K ion channels of the zebrafish heart, which determine the rate of repolarization and duration of cardiac action potential (AP) are still incompletely known and characterized. Here, we provide the first evidence for the presence of the slow component of the delayed rectifier Kchannels in the zebrafish heart and characterize electrophysiological properties of the slow component of the delayed rectifier Kcurrent, I. Zebrafish atrium and ventricle showed strong transcript expression of the kcnq1 gene, which encodes the Kv7.1 α-subunit of the slow delayed rectifier K channel. In contrast, the kcne1 gene, encoding the MinK β-subunit of the delayed rectifier, was expressed at 21 and 17 times lower level in ventricle and atrium, respectively, in comparison to the kcnq1. I was observed in 62% of ventricular myocytes with mean (± SEM) density of 1.23 ± 0.37 pA/pF at + 30 mV. Activation rate of I was 38% faster (τ = 1248 ± 215 ms) than kcnq1:kcne1 channels (1725 ± 792 ms) expressed in 3:1 ratio in Chinese hamster ovary cells. Microelectrode experiments demonstrated the functional relevance of I in the zebrafish heart, since 100 μM chromanol 293B produced a significant prolongation of AP in zebrafish ventricle. We conclude that AP repolarization in zebrafish ventricle is contributed by I, which is mainly generated by homotetrameric Kv7.1 channels not coupled to MinK ancillary β-subunits. This is a clear difference to the human heart, where MinK is an essential component of the slow delayed rectifier Kchannel.

Polyaromatic hydrocarbons in pollution: a heart‐breaking matter

“… 1 (Vornanen & Hassinen, ) 2 (Vornanen et al ., ) 3 (Dibb et al ., ) 4 (Moosmang et al ., ) 5 (Nemtsas et al ., ) 6 (Ma et al ., ) 7 (Fermini et al ., ) 8 (Noble & Tsien, ) 9 (Huang, ) 10 (European Medicines Agency, ) 11 (Warren et al ., ) 12 (Abramochkin et al ., ) 13 (Boyett, ) 14 (Bovo et al ., ) 15 (Alday et al ., ) 16 (Nakamura & Coetzee, ) 17 (Weidmann, ) 18 (Lopatin & Nichols, )…”

Polycyclic Aromatic Hydrocarbons Phenanthrene and Retene Modify the Action Potential via Multiple Ion Currents in Rainbow Trout Oncorhynchus mykiss Cardiac Myocytes

“…In fish ventricular myocytes, there are 2 major inward currents, the fast Na + current (I Na ) and L‐type Ca 2+ current (I CaL ; long‐lasting), and 2 major outward K + currents, the fast component of the delayed rectifier K + current (I Kr ) and the background inward rectifier K + current (I K1 ; Vornanen ). Besides these major ion currents, fish ventricular myocytes may have T‐type Ca 2+ current (I CaT ; transient) and the slow component of the delayed rectifier K + current (I Ks ; Nemtsas et al ; Hassinen et al ; Abramochkin et al ; Haverinen et al ). The shape of the cardiac AP is regulated by time‐ and voltage‐dependent opening and closing of the Na + , Ca 2+ , and K + channels.…”

Utility of Zebrafish Models of Acquired and Inherited Long QT Syndrome

“…molecular correlate appears to be a different inward rectifier subfamily member in zebrafish and humans (Hassinen et al, 2015;Vornanen and Hassinen, 2016). Selective drug block initially indicated little functional presence of I Ks during phase 3 repolarization in zebrafish (Nemtsas et al, 2010;Alday, 2014), however, expression of Kv7 K + transcripts in cardiac tissue (Wu et al, 2014), and more recent studies demonstrate the presence of I Ks current (Abramochkin et al, 2018). A consistent feature of zebrafish cardiac repolarization is the prominent role of I Kr in phase 3 ventricular repolarization.…”