Changes in Intracellular Na+ following Enhancement of Late Na+ Current in Virtual Human Ventricular Myocytes

The slowly inactivating or late Na+ current, INa-L, can contribute to the initiation of both atrial and ventricular rhythm disturbances in the human heart. However, the cellular and molecular mechanisms that underlie these pro-arrhythmic influences are not fully understood. At present, the major working hypothesis is that the Na+ influx corresponding to I(Na-L)significantly increases intracellular Na+, [Na]; and the resulting reduction in the electrochemical driving force for Na+ reduces and (may reverse) Na+/Ca2+ exchange. These changes increase intracellular Ca2+, [Ca2+]; which may further enhance I(Na-L)due to calmodulindependent phosphorylation of the Na+ channels. This paper is based on mathematical simulations using the O'Hara et al (2011) model of baseline or healthy human ventricular action potential waveforms(s) and its [Ca2(+)]; homeostasis mechanisms. Somewhat surprisingly, our results reveal only very small changes (<= 1.5 mM) in [Na] even when INa-L is increased 5-fold and steady-state stimulation rate is approximately 2 times the normal human heart rate (i.e. 2 Hz). Previous work done using well-established models of the rabbit and human ventricular action potential in heart failure settings also reported little or no change in [Na] when I(Na-L)was increased. Based on our simulations, the major short-term effect of markedly augmenting I(Na-L)is a significant prolongation of the action potential and an associated increase in the likelihood of reactivation of the L-type Ca2+ current, Ica-L. Furthermore, this action potential prolongation does not contribute to [Na]; increase.This work was supported by (i) the "VI Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica" from the Ministerio de Economia y Competitividad of Spain (grant number TIN2012-37546-C03-01) and the European Commission (European Regional Development Funds-ERDF-FEDER), (ii) by the Direccion General de Politica Cientifica de la Generalitat Valenciana (grant number GV/2013/119), and by (iii), Programa Prometeo (PROMETEO/2016/088) de la Conselleria d'Educacio Formacio I Ocupacio, Generalitat Valenciana. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.K Cardona; Trénor Gomis, BA.; W Giles (2016). Changes in Intracellular Na+ following Enhancement of Late Na+ Current in Virtual Human Ventricular Myocytes. PLoS ONE. 11(11). https://doi.org/10.1371/journal.pone.0167060S111

Anxiety and Depressive Symptoms Among People Living with HIV and Childhood Sexual Abuse: The Role of Shame and Posttraumatic Growth

There is a critical need to examine protective and risk factors of anxiety and depressive symptoms among people living with HIV in order to improve quality of life. Structural equation modeling was used to examine the associations between HIV-related shame, sexual abuse-related shame, posttraumatic growth, and anxiety and depressive symptoms among a cohort of 225 heterosexual women and men who have sex with men (MSM) living with HIV who have experienced childhood sexual abuse (CSA). Higher sexual abuse-related shame was related to more anxiety and depressive symptoms for heterosexual women. Higher posttraumatic growth predicted less anxiety symptoms for only heterosexual women. Higher posttraumatic growth predicted less depressive symptoms for heterosexual women and MSM, but the magnitude of this effect was stronger for heterosexual women than MSM. Psychosocial interventions may need to be tailored to meet the specific needs of heterosexual women and MSM living with HIV and CSA