Inhibition of Kv4.3 Potassium Channels by Trazodone.

Inhibition of Kv4.3 potassium channels by trazodone.

Naunyn Schmiedebergs Arch Pharmacol. 2013 Apr 25;
Chae YJ, Choi JS, Hahn SJ

Trazodone, a triazolopyridine antidepressant, is commonly used in the treatment of depression and insomnia. Kv4.3 channels are transiently, and rapidly, inactivating Kv channels that are highly expressed in cardiac myocytes and neurons. To determine the electrophysiological basis for the cardiac and neuronal actions of trazodone, we studied the effects of trazodone on Kv4.3 currents stably expressed in Chinese hamster ovary cells using the whole-cell patch-clamp technique. Trazodone decreased the peak amplitude of Kv4.3 in a concentration-dependent manner with an IC50 of 55.4 ?M. Under control conditions, the time course of inactivation of Kv4.3 at +40 mV was fitted to a double exponential function. Trazodone produced a concentration-dependent slowing of the fast and slow components of Kv4.3 inactivation during a voltage step to +40 mV. The inhibition of Kv4.3 by trazodone was voltage independent over the entire voltage range tested. Trazodone shifted the voltage dependence of the steady-state inactivation of Kv4.3 to a hyperpolarizing direction. However, the slope factor of the steady-state inactivation was not affected by trazodone. Under control conditions, the closed-state inactivation of Kv4.3 was fitted to a single exponential function. Trazodone significantly accelerated the closed-state inactivation of Kv4.3. Trazodone produced a weak use-dependent inhibition of Kv4.3 at frequencies of 1 and 2 Hz. m-Chlorophenylpiperazine (m-CPP), a major metabolite of trazodone, inhibited Kv4.3 less potently than trazodone, with an IC50 of 118.6 ?M. These results suggest that trazodone preferentially inhibited Kv4.3 by both binding to the closed state and accelerating the closed-state inactivation of the channel. HubMed – depression


A Quality of Life Survey of Individuals with Urinary Incontinence Who Visit a Self-Help Website: Implications for those Seeking Healthcare Information.

J Clin Psychol Med Settings. 2013 Apr 25;
Rozensky RH, Tovian SM, Gartley CB, Nichols TR, Layton M

Urinary Incontinence (UI) affects 200 million people worldwide with annual direct costs in the US alone estimated at $ 16.3 billion. Those with UI have reported a decrease in general quality of life with symptoms of depression, anxiety, low self-esteem, poor body image, and social stigmatization. The purpose of this study was to examine the feasibility of collecting self-reported quality of life data in a self-selected sample of individuals who visited a website providing information, education, and management suggestions regarding UI. Participants included 374 individuals with UI who responded to a solicitation for enrollment in a “Continence Comprehensive Health and Life Assessment” survey posted on The Simon Foundation for Continence website ( ). Types of problems and events associated with UI, including social connectivity and quality of life, are discussed along with limitations of the study and implications for future research. Given that 13.01 % of respondents had not spoken to a healthcare provider about their UI symptoms, 24.73 % had never seen a healthcare professional who “specializes in bladder problems,” and 75 % said they were not currently using any active approach to managing symptoms, use of such information is discussed in terms of how to construct internet healthcare information to maximize seeking appropriate healthcare services and preparing internet-based information regarding incontinence diagnosis and treatment. HubMed – depression


Structural and Functional Neuroimaging Studies in Major Depressive Disorder With Psychotic Features: A Critical Review.

Schizophr Bull. 2013 Apr 24;
Busatto GF

The relationship between major depressive disorder with psychotic (MDDP) features and schizophrenia has long been recognized, and the neurobiological boundaries between these disorders can nowadays be investigated using neuroimaging techniques. This article provides a critical review of such studies, addressing how they support a dimensional approach to the nosology and pathophysiology of psychotic disorders. A proportion of neuroimaging studies carried out to date indicate that MDDP subjects display structural and functional abnormalities in some brain regions specifically implicated in the pathophysiology of mood disorders, such as the subgenual cingulate cortex. This reinforces the validity of the classification of MDDP in proximity to major depression without psychosis. There is some neuroimaging evidence that MDDP may be associated with additional brain abnormalities relative to nonpsychotic major depression although less prominently in comparison with findings from the neuroimaging literature on schizophrenia. Brain regions seen as critical both to emotional processing and to models of psychotic symptoms, such as the hippocampus, insula, and lateral prefrontal cortex, have been implicated in separate neuroimaging investigations of either schizophrenia or major depression, as well as in some studies that directly compared depressed patients with and without psychotic features. These brain regions are key targets for future studies designed to validate imaging phenotypes more firmly associated with MDDP, as well as to investigate the relationship between these phenotypes and possible etiological influences for MDDP. HubMed – depression