Possible role of potassium channel, big K in etiology of schizophrenia.
Schizophrenia (SZ), a common severe mental disorder, affecting about 1% of the world population. However, the etiology of SZ is still largely unknown. It is believed that molecules that are in an association with the etiology and pathology of SZ are neurotransmitters including dopamine, 5-HT and gamma-aminobutyric acid (GABA). But several lines of evidences indicate that potassium large conductance calcium-activated channel, known as BK channel, is likely to be included. BK channel belongs to a group of ion channels that plays an important role in regulating neuronal excitability and transmitter releasing. Its involvement in SZ emerges as a great interest. For example, commonly used neuroleptics, in clinical therapeutic concentrations, alter calcium-activated potassium conductance in central neurons. Diazoxide, a potassium channel opener/activator, showed a significant superiority over haloperidol alone in the treatment of positive and general psychopathology symptoms in SZ. Additionally, estrogen, which regulates the activity of BK channel, modulates dopaminergic D2 receptor and has an antipsychotic-like effect. Therefore, we hypothesize that BK channel may play a role in SZ and those agents, which can target either BK channel functions or its expression may contribute to the therapeutic actions of SZ treatment.
Zhang
Lei
L
Department of Psychiatry, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814-4799, United States. leizhang@mail.nih.gov
Li
Xiaoxia
X
Zhou
Rulun
R
Xing
GuoQiang
G
D000818:Animals; D001921:Brain / Q000378:metabolism; D003981:Diazoxide / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism; D012559:Schizophrenia / Q000209:etiology* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D051036:Large-Conductance Calcium-Activated Potassium Channels; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D003981:Diazoxide; D004298:Dopamine