ABSTRACT
It is well established that alterations in cognitive function and damage to brain structures are often found in adolescents who have substance use disorder (SUD). However, deficits in executive cognitive functioning in adolescents related to the vulnerability and consumption of such substances are not well known. In this study, we use graph theoretic analysis to compare the network efficiency in the resting state for three networks-default mode network (DMN), salience network (SN) and fronto-parietal network (FPN)-between inhalant-consuming adolescents and a control group (12 to 17 years old). We analyzed whether the efficiency of these functional networks was related to working memory, mental flexibility, inhibition of response, and sequential planning. We found that, when compared to the control group, inhalant-consuming adolescents presented with important deficits in communication among brain regions that comprise the DMN, SN, and FPN networks. DMN is the most affected network by inhalant abuse during adolescence. The mediation analyses suggested that the relationship between inhalant abuse and inhibitory control and sequential planning was partly mediated by DMN efficiency.
ABSTRACT
Potassium channels allow the selective flux of K⺠excluding the smaller, and more abundant in the extracellular solution, Na⺠ions. Here we show that Shab is a typical K⺠channel that excludes Na⺠under bi-ionic, Na(o)/K(i) or Na(o)/Rb(i), conditions. However, when internal K⺠is replaced by Cs⺠(Na(o)/Cs(i)), stable inward Na⺠and outward Cs⺠currents are observed. These currents show that Shab selectivity is not accounted for by protein structural elements alone, as implicit in the snug-fit model of selectivity. Additionally, here we report the block of Shab channels by external Ca²âº ions, and compare the effect that internal K⺠replacement exerts on both Ca²âº and TEA block. Our observations indicate that Ca²âº blocks the channels at a site located near the external TEA binding site, and that this pore region changes conformation under conditions that allow Na⺠permeation. In contrast, the latter ion conditions do not significantly affect the binding of quinidine to the pore central cavity. Based on our observations and the structural information derived from the NaK bacterial channel, we hypothesize that Ca²âº is probably coordinated by main chain carbonyls of the pore's first Kâº-binding site.