The involvement of K+ channels in depression and pharmacological effects of antidepressants on these channels

Depression is a common and complex psychiatric illness with multiple clinical symptoms, even leading to the disability and suicide. Owing to the partial understanding of the pathogenesis of depressive-like disorders, available pharmacotherapeutic strategies are developed mainly based on the “monoamine hypothesis”, resulting in a limited effectiveness and a number of adverse effects in the clinical practice. The concept of multiple pathogenic factors be helpful for clarifying the etiology of depression and developing the antidepressants. It is well documented that K + channels serve crucial roles in modulating the neuronal excitability and neurotransmitter release in the brain, and abnormality of these channels participated in the pathogenic process of diverse central nervous system (CNS) pathologies, such as seizure and Alzheimer’s disease (AD). The clinical and preclinical evidence also delineates that the involvement of several types of K + channels in depressive-like behaviors appear to be evident, suggesting these channels being one of the multiple factors in the etiology of this debilitating disorder. Emerging data manifest that diverse antidepressants impact distinct K + channels, such as Kv, Kir and K 2P , meaning the functioning of these drug via a “multi-target” manner. On the other hand, the scenario of antidepressants impinging K + channels could render an alternative interpretation for the pharmacological effectiveness and numerous side effects in clinical trials. Furthermore, these channels serve to be considered as a “druggable target” to develop novel therapeutic compound to antagonize this psychiatry.