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The inward Na+ current (INa), generated by the voltage-gated Na+ channels, can be divided into two components: the fast, transient peak current (INa,peak) and the late, non-inactivating current (INa,late). INa,late plays a significant role in pathophysiology of the human heart and is a putative target for cardiovascular drugs. Because zebrafish (Danio rerio) is proposed as a potential model organism for preclinical drug screening, we decided to investigate the presence of INa,late in zebrafish ventricular myocytes. Patch-clamp experiments at +28°C and in an external saline solution containing 60 mM Na+ showed that INa,late exists in zebrafish ventricular myocytes. The density of INa,late was –0.58 ± 0.061 pA pF–1, which was 1.1 ± 0.13% of the density of the INa,peak. INa,late was increased by 10 nM Anemonia sulcata toxin 2 (ATX-II), an INa,late inducer, by 131.3 ± 17.5%. Ranolazine, an inhibitor of INa,late, reduced zebrafish ventricular INa,late and INa,peak with IC50 values of 79 and 151 µM, respectively. INa,late and INa,peak were also inhibited by tetrodotoxin (TTX) with IC50 values of 43 and 9.8 nM, respectively. The density and voltage-dependence of INa,late in zebrafish ventricular myocytes are similar to those of mammalian cardiomyocytes. On the other hand, the INa,late of zebrafish ventricular myocytes is less sensitive to ranolazine than that of mammalian cardiomyocytes, and ranolazine is less selective between INa,peak and INa,late in zebrafish than mammalian cardiomyocytes. [ABSTRACT FROM AUTHOR]

In ectotherms, compensatory changes in ion channel number and activity are needed to maintain proper cardiac function at variable temperatures. The rapid component of the delayed rectifier [K.sup.+] current ([I.sub.Kr]) is important for repolarization of cardiac action potential and, therefore, crucial for regulation of cellular excitability and heart rate. To examine temperature plasticity of cardiac [I.sub.Kr], we cloned the ether-a-go-go-related gene (ERG) channel and measured its electrophysiological properties in thermally acclimated rainbow trout (Oncorhynchus mykiss; omERG). The present findings demonstrate a complete thermal compensation in the whole cell conductance of the atrial [I.sub.Kr] in rainbow trout acclimated to 4[degrees]C (cold acclimation) and 18[degrees]C (warm acclimation). In situ hybridization indicates that transcripts of the omERG channel are present throughout the muscular tissue of the heart, and quantitative PCR shows increased expression of the omERG in cold-acclimated trout compared with warm-acclimated trout. In both acclimation groups, omERG expression is higher in atrium than ventricle. In addition, the omERG has some functional features that support [I.sub.Kr] activity at low temperatures. Voltage dependence of steady-state activation is completely resistant to temperature changes, and steady-state inactivation and activation kinetics are little affected by temperatures below 11[degrees]C. Collectively, these findings suggest that high density of cardiac [I.sub.Kr] is achieved by cold-induced increase in the number of functional omERG channels and inherent insensitivity of the omERG to temperature below 11[degrees]C. These adaptations are probably important in maintaining high heart rates and proper excitability and contractility of trout cardiac myocytes in the cold. fish heart; potassium current; temperature acclimation; cardiac action potential; excitation-contraction coupling

Genome‐wide sequencing may generate secondary findings (SFs). It is recommended that validated, clinically actionable SFs are reported back to patients/research participants. To explore publics' perspectives on the best ways to do this, we performed a vignette study among Finnish adults. Our aim was to explore how lay people react to different types of hypothetical genomic SFs. Participants received a hypothetical letter revealing a SF predisposing to a severe but actionable disease—cardiovascular disease (familial hypercholesterolemia, long QT syndrome) or cancer (Lynch syndrome, Li–Fraumeni syndrome). Participants (N = 29) wrote down their initial reactions, and discussed (N = 23) these in focus groups. Data were analyzed using inductive thematic analysis. Reactions to hypothetical SFs varied according to perceived severity and familiarity of the diseases. SFs for cancer were perceived as more threatening than for cardiovascular diseases, but less distressing than risk for psychiatric or neurological disorders, which participants spontaneously brought up. Illness severity in terms of lived experience, availability of treatment, stigma, and individual's responsibility to control risk were perceived to vary across these disease types. In addition to clinical validity and utility, SF reporting practices need to take into account potential familiarity and lay illness representations of different diseases. Illness representations may influence willingness to receive SFs, and individuals' reactions to this information. [ABSTRACT FROM AUTHOR]