Effects of metabolic inhibition on cytoplasmic calcium and contraction in smooth muscle of rat portal vein

Contractions in the rat portal vein, evoked by spontaneous action potentials or depolarizing high-K⁺ solution, are rapidly and reversibly inhibited by hypoxia or respiratory blockade. Intracellular free calcium ([Ca²⁺]_i) was measured using Fura-2 to evaluate the effects of metabolic blockade on excitation–contraction coupling. Spontaneous contractions were associated with transient increases in [Ca²⁺]_i. During exposure to cyanide (0.2–0.4 mm ) or 2,4-dinitrophenol (30 μm ) the duration and amplitude of the Ca²⁺ transients were decreased, leading to a decreased mean time integral of the individual [Ca²⁺]_i transient, and corresponding decrease in the duration and amplitude of the contraction. Basal [Ca²⁺]_i was increased in the presence of the metabolic inhibitors. High-K⁺ (40 mM) contractions caused a sustained increase in [Ca²⁺]_i, which was not inhibited by exposure to cyanide, although the amplitude of the associated contraction was greatly reduced. Together with the earlier demonstration of decreased 20 kD myosin light chain phosphorylation under these conditions, this indicates that the activation of contraction is influenced by metabolism via the energy dependence of the light chain phosphorylation reaction. Thus at least three steps in the excitation–contraction sequence are influenced by inhibition of oxidative metabolism: membrane excitation, light chain phosphorylation, and the cross-bridge cycle. This provides mechanisms for a high degree of metabolic sensitivity of vascular tone, of importance for the adaptation of blood flow to tissue metabolic demands.     

Annual Research Review: A meta-analytic review of worldwide suicide rates in adolescents

Suicide is a leading cause of death among youth worldwide. The purpose of the current review was to examine recent cross-national trends in suicide mortality rates among 10- to 19-year-olds. This study extracted suicide mortality data from the World Health Organization's (WHO) Mortality Database for the most recent year (since 2010) from any country with available high-quality data (as defined by the WHO's guidelines). Data on access to lethal means (firearms, railways) and measures of economic quality (World Bank Income Group) and inequality (Gini coefficients) were obtained from publicly available data sources. Cross-national suicide mortality rates in youth were heterogeneous. The pooled estimate across all ages, sexes, and countries was 3.77/100,000 people. The highest suicide rates were found in Estonia, New Zealand, and Uzbekistan. Suicide rates were higher among older compared with younger adolescents and higher among males than females. The most common suicide methods were hanging/suffocation and jumping/lying in front of a moving object or jumping from a height. Firearm and railway access were related to suicide deaths by firearms and jumping/lying, respectively. Economic quality and inequality were not related to overall suicide mortality rates. However, economic inequality was correlated with a higher ratio of male:female suicides. This study provides a recent update of cross-national suicide trends in adolescents. Findings replicate prior patterns related to age, sex, geographic region, and common suicide methods. New to this review are findings relating suicide method accessibility to suicide mortality rates and the significant association between income inequality and the ratio of male:female suicide. Future research directions include expanding the worldwide coverage to more low- and middle-income countries, examining demographic groupings beyond binary sex and to race/ethnicity within countries, and clarifying factors that account for cross-national differences in suicide trends.