Domesticated HERV-W env contributes to the activation of the small conductance Ca^(2+)-activated K^(+)type 2 channels via decreased 5-HT4 receptor in recent-onset schizophrenia

The human endogenous retroviruses type W family envelope(HERV-W env)gene is located on chromosome 7q21-22.Our previous studies show that HERV-W env is elevated in schizophrenia and HERV-W env can increase cal-cium influx.Additionally,the 5-HTergie system and particularly 5-hydroxytryptamine(5-HT)receptors play a prominent role in the pathogenesis and treatment of schizophrenia.5-hydroxytryptamine receptor 4(5-HT4R)agonist can block calcium channels.However,the underlying relationship between HERV-W env and 5-HT4R in the etiology of schizophrenia has not been revealed.Here,we used enzyme-linked immunosorbent assay to detect the concentration of HERV-W env and 5-HT4R in the plasma of patients with schizophrenia and we found that there were decreased levels of 5-HT4R and a negative correlation between 5-HT4R and HERV-W env in schizophrenia.Overexpression of HERV-W env decreased the transcription and protein levels of 5-HT4R but increased small conductance Ca^(2+)-activated K^(+)type 2 channels(SK2)expression levels.Further studies revealed that HERV-w env could interact with 5-HT4R.Additionally,luciferase assay showed that an essential region(-364 to-176 from the transcription start site)in the SK2 promoter was required for HERV-W env-induced SK2 expression.Importantly,5-HT4R participated in the regulation of SK2 expression and promoter activity.Electrophysiological recordings suggested that HERV-Wenv could increase SK2 channel currents and the increase of SK2 currents was inhibited by 5-HT4R.In condusion,HERV-W env could activate SK2 channels via decreased 5-HT4R,which might exhibit a novel mechanism for HERV-Wenv to influence neuronal activity in schizophrenia.

Intermediate conductance, Ca^2＋-activated K^＋ channels： a novel target for chronic renal diseases

Renal failure is a medical condition in which the kidneys are not working properly. There are two types of kidney failure： 1） acute kidney failure, which is sudden and often reversible with adequate treatment; and 2） chronic renal failure, which develops slowly and often is not reversible. The last stage of chronic renal failure is fatal without dialysis or kidney transplant. The treatment for chronic renal failure is focusing on slowing the progression of kidney damage. Several reports have described a promising approach to slow the loss of renal function through inhibition of the basolateral membrane, Ca^2＋-activated K^＋ （KCa3.1） channel with a selective and nontoxic blocker TRAM-34. This review summarizes pathophysiological studies that describe the role of KCa3.1 in kidney diseases.

otassium channels in airway smooth muscle and airway hyperreactivity in asthma

Our knowledge of the physiology of ion channels has increased tremendously during the past 20 years because of the advances of the single-channel recording and molecular cloning techniques. More than 50 different identified potassium channels have already been found.1,2 They are distributed ubiquitously in wide variety of cells including airway smooth muscle （ASM） cells and inflammatory cells in airway such as eosinophils, basophils, macrophages and so on.3 Several types of K+ channels have been identified in ASM cells, e.g., a large-conductance, voltgage-dependent Ca2+-activated K+ channel(BKCa), a voltage-dependent delayed-rectifier K+ channel（Kv）, and an ATP-sensitve K+ channel(KATP).1 In such excitable cells,