Potassium Ion Channel Protein (KCNH) Levels in Patients with Fibromyalgia Syndrome.

Although there is not yet full clarity of the pathogenesis of fibromyalgia syndrome (FM), central sensitization is considered to be responsible. The purpose of this study was to measure the plasma levels of potassium ion channel proteins (human KCNH2, KCNH6 and KCNH7) in FM patients and healthy control subjects. The study sample includes 76 newly diagnosed FM patients and 79 healthy individuals. Venous blood samples were taken to measure the plasma levels of KCNH2, KCNH6 and KCNH7. Pain severity in FM patients was assessed using a visual analog scale (VAS). Bioinformatics analysis was performed using the STRING v 11 Protein interaction tool. Age, gender and body mass index were seen to be similar in both groups. In comparisons between FM and control groups, KCNH2 plasma levels was found to be significantly lower in the FM group. No significant correlation was found between plasma levels of KCNH2, KCNH6 and KCNH7 protein levels and VAS score of patients with FM. The KCNH2 protein had a high homology score with 9 proteins. The plasma levels of KCNH2 FM patients were found to be lower than those of the healthy control subjects, no difference was determined in respect of the plasma levels of KCNH6 and KCNH7. These results may be of use in guiding future studies on the pathogenesis of FM.

Observations on conducting whole-cell patch clamping of the hERG cardiac K+ channel in pure human serum.

Inhibition of the human ether-a-go-go-related gene (hERG) K+ channel by drugs leads to QT prolongation on the electrocardiogram and can result in serious cardiac arrhythmia. For this reason, screening of drugs on hERG is mandatory during the drug development process. Patch clamp electrophysiology in a defined physiological saline solution (PSS) represents the standard method for assaying drug effects on the channel. To make the assay more translatable to clinical studies, we have conducted whole-cell patch clamping of hERG using pure human serum as the extracellular medium. Pure human serum had little effect on the hERG channel waveform or the current-voltage relationship when compared to PSS. hERG current recordings were highly stable in serum at room temperature, but prolonged recordings at the physiological temperature required prior heat inactivation of the serum. Compared to PSS, the IC50 values, conducted at room temperature, of the classic hERG blocking drugs cisapride, moxifloxacin, and terfenadine were shifted to the right by an extent predicted by their known plasma protein binding, but we did not detect any differences in IC50 s between male and female serum. Total plasma levels of these drugs associated with clinical QT prolongation corresponded to small (<15%) inhibition of hERG current in pure serum suggesting that minor inhibition of the channel leads to observable pharmacodynamic effects. Conducting whole-cell patch clamping of hERG in human serum has the potential to make the assay more translatable to clinical studies and improve its predictive value for safety testing. Copyright © 2016 John Wiley & Sons, Ltd.

Circulating KCNH2 current-activating factor in patients with heart failure and ventricular tachyarrhythmia.

BACKGROUND: It is estimated that approximately half of the deaths in patients with HF are sudden and that the most likely causes of sudden death are lethal ventricular tachyarrhythmias such as ventricular tachycardia (VT) or fibrillation (VF). However, the precise mechanism of ventricular tachyarrhythmias remains unknown. The KCNH2 channel conducting the delayed rectifier K(+) current (I(Kr)) is recognized as the most susceptible channel in acquired long QT syndrome. Recent findings have revealed that not only suppression but also enhancement of I(Kr) increase vulnerability to major arrhythmic events, as seen in short QT syndrome. Therefore, we investigated the existence of a circulating KCNH2 current-modifying factor in patients with HF. METHODOLOGY/PRINCIPAL FINDINGS: We examined the effects of serum of HF patients on recombinant I(Kr) recorded from HEK 293 cells stably expressing KCNH2 by using the whole-cell patch-clamp technique. Study subjects were 14 patients with non-ischemic HF and 6 normal controls. Seven patients had a history of documented ventricular tachyarrhythmias (VT: 7 and VF: 1). Overnight treatment with 2% serum obtained from HF patients with ventricular arrhythmia resulted in a significant enhancement in the peaks of I(Kr) tail currents compared to the serum from normal controls and HF patients without ventricular arrhythmia. CONCLUSIONS/SIGNIFICANCE: Here we provide the first evidence for the presence of a circulating KCNH2 channel activator in patients with HF and ventricular tachyarrhythmias. This factor may be responsible for arhythmogenesis in patients with HF.