Ionic current changes underlying action potential repolarization responses to physiological pacing and adrenergic stimulation in adult rat ventricular myocytes

This study aimed to simulate ventricular responses to elevations in myocyte pacing and adrenergic stimulation using a novel electrophysiological rat model and investigate ion channel responses underlying action potential (AP) modulations. Peak ion currents and AP repolarization to 50% and 90% of full repolarization (APD50-90) were recorded during simulations at 1–10 Hz pacing under control and adrenergic stimulation conditions. Further simulations were performed with incremental ion current block (L-type calcium current, ICa; transient outward current, Ito; slow delayed rectifier potassium current, IKs; rapid delayed rectifier potassium current, IKr; inward rectifier potassium current, IK1) to identify current influence on AP response to exercise. Simulated APD50-90 closely resembled experimental findings. Rate-dependent increases in IKs (6%–101%), IKr (141%–1339%), and ICa (0%–15%) and reductions in Ito (11%–57%) and IK1 (1%–9%) were observed. Meanwhile, adrenergic stimulation triggered moderate increases in all currents (23%–67%) except IK1. Further analyses suggest AP plateau is most sensitive to modulations in Ito and ICa while late repolarization is most sensitive to IK1, ICa, and IKs, with alterations in IKs predominantly stimulating the greatest magnitude of influence on late repolarization (35%–846% APD90 prolongation). The modified Leeds rat model (mLR) is capable of accurately modeling APs during physiological stress. This study highlights the importance of ICa, Ito, IK1, and IKs in controlling electrophysiological responses to exercise. This work will benefit the study of cardiac dysfunction, arrythmia, and disease, though future physiologically relevant experimental studies and model development are required

Exploring Links between Neuroticism and Psychoticism Personality Traits, Attentional Biases to Threat and Friendship Quality in 9-11-year-olds

The current study used an eye-movement Remote Distractor Paradigm (RDP) to explore attention to threat and considered associations with personality traits (neuroticism and psychoticism) and self-reported friendship quality in children aged 9–11 years. The RDP asked children to look at and identify a target presented on a computer display in the presence or absence of a central, parafoveal or peripheral visual distractor (an angry, happy or neutral face). The results showed that symptoms of neuroticism were associated with hypervigilance for threat (i.e., slower latencies to initiate eye movements to the target in the presence of angry versus happy or neutral faces). In addition, when distractors were presented centrally, this relationship was most evident in children who reported lower levels of attentional control. Psychoticism traits were associated with increased selective attention to all distractors (as measured by directional errors to face stimuli) and to child reported lower friendship quality. Moreover, the negative relationship between psychoticism and friendship characteristics associated with companionship was mediated via attentional capture of threat (i.e., a greater proportion of directional errors to angry distractors). The findings have potential to inform the development of translational research, to reduce symptoms of psychopathology and address attentional biases to threat with an aim to improve peer relationships in late childhood