Associate editor: T.C. NapierIon channels and intracellular signaling proteins as potential targets for novel therapeutics for addictive and depressive disorders
Section snippets
General introduction
Modern neuroscience is placing increased emphasis on understanding how molecules in the brain affect behavior. An improved understanding of the brain and the biological bases of conditions such as addictive and depressive disorders is important because it should ultimately enable the design of innovative treatments for these conditions. The development of rational therapies that are based on knowledge of what is different about the addicted or depressed brain would be an important advance,
Ion channels as therapeutic targets for substance abuse
Ion channels are the basic, essential effectors that allow neurons to modulate the various aspects of their short- and long-term excitability. They are classified and named sodium, potassium, calcium, and chloride channels based on the main type of ion to which they are permeable (Hille, 2001). Ion channels present a high degree of functional specificity depending on many factors, such as voltage dependence, conductance properties, ligand specificity, and subunit composition. This specificity
Intracellular signaling molecules
Alterations in ion channel function affect intracellular signal transduction systems. Events on the cell surface (e.g., stimulation of glutamate receptors or G-protein-coupled receptors) can directly or indirectly affect ion flux through ionotropic receptors or channels (Fig. 1). Increased Ca2+ influx is one of several events that can trigger intracellular signaling cascades that result in alterations in the activity of transcription factors and, in turn, gene transcription. Localized within
Summary and conclusions
Neurology and psychiatry are entering a new phase in which basic research is beginning to identify molecules that are involved in causing aberrant behaviors. A better understanding of the molecular adaptations that lead to the development or expression of addictive or depressive-like behaviors should soon lead to significant improvements in the diagnosis and treatment of a variety of debilitating conditions in humans. It has become clear that key aspects of conditions such as addiction or mood
Acknowledgments
We apologize to authors whose work could not be cited due to space limitations. We thank Anjlee Mahajan for proofreading. Our research is supported by the State of California for medical research on alcohol and substance abuse through the University of California, San Francisco (AB), DA12736 (to WC), and MH63266 (to WC).
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BK Channels: mediators and models for alcohol tolerance
2009, Trends in NeurosciencesCitation Excerpt :As with other ion channels, the activity of BK splice variants is controlled in part by kinases and phosphatases [15,70–73]. Recent studies have made clear how post-translational modifications such as phosphorylation/dephosphorylation can control the response to alcohol [74–77], as well as provide a potentially elegant mechanism for tolerance. Thus, a recent study demonstrated that the calcium/calmodulin-dependent protein kinase, CaMKII, is crucial in the effects of alcohol on the BK channel α subunit.
The ibogaine medical subculture
2008, Journal of EthnopharmacologyA novel proline-rich M-superfamily conotoxin that can simultaneously affect sodium, potassium and calcium currents
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