Objective To study the effect of allitridum on the transient outward potassium current （Ito） of ventricular myocytes in heart failure （HF）. Methods The dual enzymatic method was used to separate single ventricular myocytes from Sprague Dawley rats. Patch-clamping was used to record Ito and analyze the effect of allitridum on the current. Results The Ito current had a significant decrease in the HF group, compared with the control group. The density of Ito in the HF group was increased after treatment of allitridum （30 μmol/L）. The peak current densities of Ito were enhanced in the HF group from 6.01 ±0.30 pA/pF to 8.41 ±0.54 pA/pF （P 〈 0.01） at ＋50 mV after treatment with allitridum （30 μmol/L）. We also determined the effect of allitridum on the gating mechanism of the Ito in the HF group. Conclusions We found that allitridum increased the Ito by accelerating the activation of channels and shortened the time constants of inactivation, and allitridum decreased the remodeling of Ito in ventricular myocytes of rats with HF.
Objectives To evaluate the association between a KCNQ 1 mutation, R259H, and short QT syndrome （SQTS） and to explore the elec- trophysiological mechanisms underlying their association. Methods We performed genetic screening of SQTS genes in 25 probands and their family members （63 patients）. We used direct sequencing to screen the exons and intron-exon boundaries of candidate genes that en- code ion channels which contribute to the repolarization of the ventricular action potential, including KCNQI, KCNH2, KCNE1, KCNE2, KCNJ2, CACNAlc, CACNB2b and CACNA2D1. In one of the 25 SQTS probands screened, we discovered a KCNQ1 mutation, R259H. We cloned R259H and transiently expressed it in HEK-293 cells; then, currents were recorded using whole cell patch clamp techniques. Results R259H-KCNQ 1 showed significantly increased current density, which was approximately 3-fold larger than that of wild type （WT） after a depolarizing pulse at 1 s. The steady state voltage dependence of the activation and inactivation did not show significant differences between the WT and R259H mutation （P 〉 0.05）, whereas the time constant of deactivation was markedly prolonged in the mutant compared with the WT in terms of the test potentials, which indicated that the deactivation of R259H was markedly slower than that of the WT. These results suggested that the R259H mutation can effectively increase the slowly activated delayed rectifier potassium current （Irs） in phase 3 of the cardiac action potential, which may be an infrequent cause of QT interval shortening. Conclusions R259H is a gain-of-function muta- tion of the KCNQ1 channel that is responsible for SQTS2. This is the first time that the R259H mutation was detected in Chinese people.
Zhi-Juan WUYun HUANGYi-Cheng FUXiao-Jing ZHAOChao ZHUYu ZHANGBin XUQing-Lei ZHUYang LI
