血栓烷A_2类似物对大鼠肺动脉血管平滑肌细胞钾离子通道表达的影响

目的:观察血栓烷A2(TXA2)类似物U46619对实验大鼠肺动脉血管平滑肌细胞(PASMCs)K+通道Kv1.2、Kv1.5、Kv2.1蛋白质和mRNA表达的影响。方法:采用酶法分离、培养Wistar大鼠PASMCs,通过Western-blot和RT-PCR方法分别从蛋白质水平和mRNA水平分析U46619对Kv1.2、Kv1.5、Kv2.1表达的抑制作用。结果:100nmol/LU46619对Kv1.2表达有明显抑制作用。结论:TXA2类似物U46619可能通过抑制Kv1.2表达而参与大鼠肺动脉血管的收缩。     

Subacute hypoxia decreases voltage-activated potassium channel expression and function in pulmonary artery myocytes

Chronic hypoxia results in both structural changes in the pulmonary artery and a sustained increase in pulmonary vascular tone. This study investigated the effects of subacute moderate hypoxia on expression and function of potassium (K+) channels in rat pulmonary artery myocytes (PASMCs). The rats were kept at 0.67 atmospheres for 6, 12, or 24 h. We found that the expression of mRNA for voltage-activated K+ channels (Kv)1.2, Kv1.5, and Kv2.1 is reduced after less than 24 h of this moderate hypoxia. K+ current (Ik) is significantly inhibited in PASMCs from rats hypoxic for 24 h, resting membrane potential is depolarized and cytosolic [Ca2+] is increased in these cells. In addition, antibodies to Kv1.2, Kv1.5, and Kv2.1 inhibit Ik, cause membrane depolarization and attenuate both hypoxia- and 4-AP-induced elevation in [Ca2+]i in PASMCs from normoxic rats but not from 24 h hypoxic rats. Subacute hypoxia does not completely remove the mRNA for Kv1.2, Kv1.5, and Kv2.1, but antibodies against these channels no longer alter Ik or cytosolic calcium, suggesting that subacute hypoxia may inactivate the channels as well as reduce expression. As the expression of mRNA for Kv1.2, Kv1.5, and Kv2.1 is sensitive to subacute hypoxia and decreased expression/function of these channels has physiologic effects on membrane potential and cytosolic calcium, it seems likely that these Kv channels may also be involved in the mechanism of high-altitude pulmonary edema and possibly in the signaling of chronic hypoxic pulmonary hypertension.     

Kv1.2、Kv1.5、Kv2.1钾通道在缺氧性肺血管收缩中的作用

目的和方法:雄性Wistar大鼠随机分为两组:常氧对照组和低氧组。用酶消化的方法获得单个大鼠肺内动脉平滑肌细胞(PASMC)。采用全细胞膜片钳技术,记录PASMC静息膜电位(Em)和电压门控性钾通道电流(IKv),通过细胞内灌流Kv1.2/Kv1.5/Kv2.1抗体混合液(1∶125),探讨Kv1.2、Kv1.5、Kv2.1钾通道在缺氧性肺血管收缩(HPV)中的作用。结果:①低氧组膜电位明显去极化,由(-51.8±0.8) mV 去极到(-47.2± 0.7) mV,P<0.01,IKv与常氧组相比显著降低,在测试电压-30 mV时, IKv由(6.16±0.58) pA/pF 降为 (3.31±0.37) pA/pF (P<0.01)。②细胞内灌流Kv1.2/Kv1.5/Kv2.1抗体混合液可显著抑制常氧对照组PASMC 的IKv,使Em去极化,然而细胞内灌流Kir2.1/Kir2.3/Kir4.1(1∶125)抗体混合液对常氧对照组PASMC 的IKv和Em无显著影响。③细胞内灌流Kv1.2/Kv1.5/Kv2.1抗体混合液和Kir2.1/Kir2.3/Kir4.1抗体混合液对低氧组PASMC的IKv和Em均无显著影响。结论:Kv1.2、Kv1.5、Kv2.1可能是氧敏感型通道,并介导了低氧性肺血管收缩。     

慢性阻塞性肺疾病合并慢性缺氧患者肺动脉平滑肌细胞电压门控钾通道亚型基因表达的变化

目的：探讨人肺动脉平滑肌细胞（PASMCs）的几种Kv通道亚型：Kv1.2、 Kv1.3、Kv1.5、Kv2.1、Kv3.1等，在COPD合并慢性缺氧时基因表达的变化。旨在探索预防人类肺源性心脏病的发生和找到新的防治方法提供试验依据。 方法： 从手术室切取人正常肺组织、单纯COPD患者和COPD合并慢性缺氧患者肺组织，将标本分为：①正常对照的PASMCs、单纯COPD和COPD合并慢性缺氧患者的PASMCs；②正常对照的PASMCs和经过慢性缺氧培养的PASMCs。利用半定量RT-PCR技术，分析Kv1.2、Kv1.3、Kv1.5、Kv2.1、Kv3.1等的基因表达。 结果： ①Kv1.2、Kv1.3、Kv1.5、Kv2.1、Kv3.1等基因在正常PASMCs和单纯COPD患者PASMCs中均有表达，而且两者无显著差异；②Kv1.2、Kv1.5、Kv2.1在患者在体慢性缺氧和离体慢性缺氧时的表达均明显降低（P<0.05）；Kv1.3在患者在体慢性缺氧时表达明显降低（P<0.05），而离体慢性缺氧时无显著变化（P>0.05）；Kv3.1在患者在体慢性缺氧和离体慢性缺氧时的表达均无显著变化（P>0.05）；③Kv1.2、Kv1.5、Kv2.1、Kv3.1等基因在单纯COPD时表达显著上调（P<0.05）。 结论： 在慢性缺氧情况下，Kv1.2、Kv1.3、Kv1.5、Kv2.1 4种亚型基因表达明显下降，提示可能在促进人肺动脉高压的形成和发展中起重要作用。而慢性缺氧对Kv3.1基因表达无显著影响，提示它们可能对缺氧不敏感，在人肺动脉高压发生中处于次要地位。至于在单纯COPD时几种亚型的表达上调，原因不清楚，需进一步研究证实。     

慢性低氧对大鼠肺组织电压门控钾通道表达的影响

目的:探讨慢性低氧对大鼠肺组织电压门控钾通道亚型Kv1.5、Kv2.1、Kv9.3表达的影响。方法:将12只Wistar大鼠随机分为对照组和慢性低氧组,每组6只。采用RT-PCR和Westernblot对大鼠肺组织匀浆中Kv1.5、Kv2.1、Kv9.3mRNA和Kv1.5蛋白质的表达进行观察。结果:慢性低氧组大鼠肺组织匀浆中Kv1.5、Kv2.1、Kv9.3mRNA和Kv1.5蛋白质表达明显低于对照组(P<0.01)。结论:慢性低氧可以从转录、翻译两个水平抑制大鼠肺组织中Kv1.5、Kv2.1Kv9.3的表达,Kv1.5、Kv2.1、Kv9.3表达的减少必将导致Kv数目的减少和电流的降低。Kv1.5、Kv2.1、Kv9.3可能是氧敏感钾通道亚型。     

Hypoxia suppresses Kv 2.1 channel expression through endogenous 15-hydroxyeicosatetraenoic acid in rat pulmonary artery

We have previously reported that hypoxia activates lung 15-lipoxygenase (15-LOX), which catalyzes arachidonic acid to produce 15-HETE, leading to constriction of neonatal rabbit pulmonary arteries. Hypoxia suppresses Kv2.1 channel expression. Although the Kv channel inhibition by hypoxia is likely to be mediated through 15-HETE, direct evidence is still lacking. To explore whether 15-LOX/15-HETE pathway contributes to the hypoxia-induced down-regulation of Kv2.1 channel, we performed studies using 15-LOX blockers, semi-quantitative PCR and western blot analysis. We found that Kv2.1 channel expression at the mRNA and protein levels was greatly up-regulated in pulmonary arterial smooth muscle cells (PASMCs) and pulmonary artery (PA) after blockade of endogenous 15-HETE under hypoxic condition. 15-HETE further decreased Kv2.1 channel expression in comparison with 12-HETE and 5-HETE in cultured PASMCs and PA under normoxic conditions. These data indicate that hypoxia suppresses Kv2.1 channel expression through endogenous 15-HETE in PA.     

BQ123对大鼠肺动脉平滑肌细胞电压门控钾通道表达的影响

目的：探讨内皮素-1受体拮抗剂BQ123 对大鼠肺动脉平滑肌细胞电压门控钾通道亚型基因表达的影响。 方法： 根据常氧 (PO2 152 mmHg ) 及慢性低氧（PO2 40±5 mmHg）的不同培养条件，将肺动脉平滑肌细胞分为常氧组和慢性低氧组，并用BQ123分别处理上述两组细胞，采用半定量RT-PCR技术检测大鼠肺动脉平滑肌细胞Kv2.1、Kv9.3基因表达的变化。 结果： 经过慢性低氧，大鼠肺动脉平滑肌细胞Kv2.1、Kv9.3的mRNA表达水平明显低于常氧组（P<0.01，n=5），BQ123对常氧组Kv2.1的mRNA表达无影响（P>0.05，n=5），但可明显增加慢性低氧组Kv2.1的表达（P<0.01，n=5）。无论在常氧还是慢性低氧时，BQ123对Kv9.3的mRNA表达均无影响（P>0.05，n=5）。 结论： 慢性低氧可降低大鼠肺动脉平滑肌细胞电压门控钾通道的表达，内皮素-1受体拮抗剂BQ123可能通过抑制PASMCs的增殖，改变了细胞内信号转导通路中某些因子的表达，从而间接促进Kv的表达。     

慢性吸烟大鼠肺动脉平滑肌细胞钾通道Kv1.5、BKCa表达的变化

目的：观察吸烟对大鼠肺动脉平滑肌大电导的钙激活的钾通道（BK_Ca）和电压依赖性延迟整流钾通道Kv1.5蛋白和mRNA表达的影响，以阐明吸烟引起的肺血管反应性改变中钾通道表达的变化。方法：复制大鼠的慢性吸烟模型，采用HE染色、免疫组织化学染色、原位杂交等方法。结果：（1）慢性吸烟可降低大鼠肺动脉平滑肌 BK_Ca 蛋白和mRNA表达；（2）慢性吸烟可降低大鼠肺动脉平滑肌Kv1.5蛋白和mRNA表达；（3）大动脉 BK_Ca的降低程度大于Kv1.5，小动脉 BK_Ca和Kv1.5的降低程度无明显差异。结论：慢性吸烟可下调大鼠肺动脉平滑肌钾通道 BK_Ca和Kv1.5的表达水平，是导致肺血管反应性增高的机制之一。     

Functional changes in genetically dysmyelinated spinal cord axons of shiverer mice: role of juxtaparanodal Kv1 family K+ channels

Axonal dysfunction after spinal cord injury (SCI) and other types of neurotrauma is associated with demyelination and exposure of juxtaparanodal K+ channels. In this study, sucrose gap electrophysiology using selective and nonselective K+ channel blockers, confocal immunohistochemistry, and Western blotting were used to study the role of Kv1.1 and Kv1.2 K+ channel subunits in dysmyelination-induced spinal cord axonal dysfunction in shiverer mice, which lack the gene encoding myelin basic protein (MBP) and exhibit incomplete myelin sheath formation on CNS axons. The shiverer spinal cord axons exhibited smaller amplitude of compound action potentials (CAPs), reduced conduction velocity, reduced excitability, and greater degree of high-frequency conduction failure. The "fast" K+ channel blocker 4-aminopyridine, the toxin DTX-I, which targets the Kv1.1 and Kv1.2, but not DTX- K, which has higher selectivity for Kv1.1, increased the amplitude and area of CAPs of shiverer mice spinal cord axons but had insignificant effects in wild-type mice. Confocal immunohistochemistry showed that, unlike wild-type mice, which have a precise juxtaparanodal localization of the Kv1.l and Kv1.2 K+ channel subunits, shiverer mouse axons displayed a dispersed distribution of these subunits along the internodes. In contrast, the Kv1.l and Kv1.2 subunits, Na+ channels remained highly localized to the nodal regions. Western blotting showed an increased expression of Kv 1.1 and 1.2 in the shiverer mouse spinal cord. These results provide evidence that the neurological deficits associated with myelin deficiency reflect the altered distribution and expression of the K+ channel subunits Kv1.l and Kv1.2 along the internodes of spinal cord axons associated with the biophysical consequences caused by alterations in the myelin sheaths.     

Adaptative modifications of right coronary myocytes voltage-gated K+ currents in rat with hypoxic pulmonary hypertension

Chronic hypoxia (CH)-induced pulmonary hypertension (PHT) is well known to alter K+ channels in pulmonary myocytes. PHT induces right ventricle hypertrophy that increases oxygen demand; however, coronary blood flow and K+ channel adaptations of coronary myocytes during PHT remain unknown. We determined whether CH and PHT altered K+ currents and coronary reactivity and what impact they might have on right myocardial perfusion. Right ventricle perfusion, as attested by microspheres, was redistributed toward hypertrophied right ventricle [RV/LV (%)=0.59+/-0.07% in CH rats vs. 0.29+/-0.03 in control rats, P<0.05]. Whole-cell patch clamping showed a reduction of global outward current in hypoxic right coronary artery myocytes (H-RCA), whereas hypoxic left coronary artery myocytes exhibited an increase. K+ channel blockers revealed that a 4-aminopyridine (4AP)-sensitive current (Kv current) was decreased in H-RCA (14.3+/-1.1 vs. 23.4+/-2.5 pA/pF at 60 mV in control RCA, P<0.05) and increased in hypoxic left coronary artery myocytes (H-LCA; 26.4+/-3.8 vs. 11.8+/-1.6 pA/pF at 60 mV in control LCA, P<0.05). Constriction to 4AP was decreased in H-RCA when compared to normoxic control and increased in H-LCA when compared to LCA. Finally, we observed that the expression of Kv1.2 and Kv1.5 were lower in H-RCA than that in H-LCA. This study reveals that CH differentially regulates Kv channels in coronary myocytes. Hypoxia decreases Kv currents and therefore reduces vasoreactivity that contributes to an adaptative response leading to right hypertrophied ventricle perfusion enhancement at rest.     

Altered expression of potassium channel subunit mRNA and alpha-dendrotoxin sensitivity of potassium currents in rat dorsal root ganglion neurons after axotomy

Previous studies have raised the possibility that a decrease in voltage-gated K+ currents may contribute to hyperexcitability of injured dorsal root ganglion (DRG) neurons and the emergence of neuropathic pain. We examined the effects of axotomy on mRNA levels for various Kv1 family subunits and voltage-gated K+ currents in L4-L5 DRG neurons from sham-operated and sciatic nerve-transected rats. RNase protection assay revealed that Kv1.1 and Kv 1.2 mRNAs are highly abundant while Kv1.3, Kv1.4, Kv1.5 and Kv1.6 mRNAs were detected at lower levels in L4-L5 DRGs from sham and intact rats. Axotomy significantly decreased Kv1.1, Kv1.2, Kv1.3 and Kv1.4 mRNA levels by approximately 35%, approximately 60%, approximately 40% and approximately 80%, respectively, but did not significantly change Kv1.5 or Kv1.6 mRNA levels. Patch clamp recordings revealed two types of K+ currents in small-sized L4-L5 DRG neurons: sustained delayed rectifier currents elicited from a -40 mV holding potential and slowly inactivating A-type currents that was additionally activated from a -120 mV holding potential. Axotomy decreased both types of K+ currents by 50-60% in injured DRG neurons. In addition, axotomy increased the alpha-dendrotoxin sensitivity of the delayed rectifier, but not slow A-type K+ currents in injured DRG neurons. These results suggest that Kv1.1 and Kv1.2 subunits are major components of voltage-gated K+ channels in L4-L5 DRG neurons and that the decreased expression of Kv1-family subunits significantly contributes to the reduction and altered kinetics of Kv current in axotomized neurons.     

Kv1.5对大鼠低氧高二氧化碳性PASMCs增殖、凋亡的影响及与MAPK通路的关系

 目的：探讨电压依赖性钾离子通道Kv1.5对大鼠低氧高二氧化碳性肺动脉平滑肌细胞（PASMCs）增殖、凋亡的影响及其与丝裂原激活蛋白激酶（MAPK）信号通路的关系。方法：体外培养大鼠PASMCs,复制低氧高二氧化碳模型,随机分组如下：常氧组（N组）;低氧高二氧化碳组（HH组）;低氧高二氧化碳+溶剂DMSO对照组（HD组）;低氧高二氧化碳+ERK1/2通路抑制剂U0126组（HU组）;低氧高二氧化碳+p38 MAPK通路抑制剂SB203580组（HS组）;低氧高二氧化碳+MAPK通路激动剂茴香霉素（anisomycin）组（HA组）。采用CCK-8法检测细胞活性,蛋白免疫印迹法检测Kv1.5、增殖细胞核抗原（PCNA）及Bax蛋白的表达水平。结果：与N组相比,HH组和HD组细胞活性增加（P<0.01）,PCNA蛋白表达上调,Kv1.5及Bax蛋白表达均明显降低（P<0.01）,HH组和HD组间各指标变化均无显著差异（均P>0.05）;较之HD组,HU组、HS组及HA组细胞活性降低（P<0.05或P<0.01）,PCNA蛋白表达下调,Kv1.5及Bax蛋白表达均明显增加,差异均显著（P<0.01）,其中以HA组各指标变化最明显。结论：钾离子通道Kv1.5对低氧高二氧化碳性大鼠PASMCs增殖、凋亡的调节可能与MAPK通路的激活有关。     

Characterization of the heteromeric potassium channel formed by kv2.1 and the retinal subunit kv8.2 in Xenopus oocytes

Kv8.2 (KCNV2) subunits do not form homotetrameric potassium channels, although they coassemble with Kv2.1 to constitute functional heteromers. High expression of Kv8.2 was reported in the human retina and its mutations were linked to the visual disorder "cone dystrophy with supernormal rod electroretinogram." We detected abundant Kv8.2 expression in the photoreceptor layer of mouse retina, where Kv2.1 is also known to be present. When the two subunits were coexpressed in Xenopus oocytes in equal amounts, Kv8.2 abolished the current of Kv2.1. If the proportion of Kv8.2 was reduced then the current of heteromeric channels emerged. Kv8.2 shifted the steady-state activation of Kv2.1 to more negative potentials, without affecting the voltage dependence of inactivation. This gave rise to a window current within the -40 to -10 mV membrane potential range. Ba2+ inhibited the heteromeric channel and shifted its activation to more positive potentials. These electrophysiological and pharmacological properties resemble those of the voltage-gated K+ current (named I Kx) described in amphibian retinal rods. Furthermore, oocytes expressing Kv2.1/Kv8.2 developed transient hyperpolarizing overshoots in current-clamp experiments, whereas those expressing only Kv2.1 failed to do so. Similar overshoots are characteristic responses of photoreceptors to light flashes. We demonstrated that Kv8.2 G476D, analogous to a disease-causing human mutation, eliminated Kv2.1 current, if the subunits were coexpressed equally. However, Kv8.2 G476D did not form functional heteromers under any conditions. Therefore we suggest that the custom-tailored current of Kv2.1/Kv8.2 functionally contributes to photoreception, and this is the reason that mutations of Kv8.2 lead to a genetic visual disorder.     

羟基红花黄色素A通过激活Kv通道舒张大鼠冠状动脉

目的:研究羟基红花黄色素A (hydroxysafflor yellow A,HSYA)对离体大鼠冠状动脉(rat coronary artery,RCA)的舒张作用,并探讨该作用与电压门控性钾通道(Kv通道)的关系。方法:采用DMT离体血管环技术明确HSYA对RCA的肌源性作用及血管内皮对该作用的影响;采用全细胞膜片钳技术观察HSYA对RCA平滑肌细胞Kv电流的影响;采用Western blot技术探讨HSYA对RCA平滑肌细胞Kv1.2和Kv1.5通道蛋白表达的影响。结果:10μmol/L和30μmol/L HSYA能够舒张60 mmol/L KCl或0.1 mmol/L U46619预收缩的RCA(P<0.05),但其对预收缩的内皮完整组和去内皮组RCA舒张作用的差异无统计学显著性(P>0.05);HSYA(3μmol/L、10μmol/L和30μmol/L)可使RCA平滑肌细胞Kv电流显著增加(P<0.05);10μmol/L和30μmol/L HSYA能够增加RCA平滑肌细胞Kv1.2和Kv1.5通道蛋白的表达。结论:HSYA可舒张预收缩的RCA,该作用与血管内皮无关,其可能的机制与增强Kv通道功能和蛋白表达有关。     

VAMP2 interacts directly with the N terminus of Kv2.1 to enhance channel inactivation

Recently, we demonstrated that the Kv2.1 channel plays a role in regulated exocytosis of dense-core vesicles (DCVs) through direct interaction of its C terminus with syntaxin 1A, a plasma membrane soluble NSF attachment receptor (SNARE) component. We report here that Kv2.1 interacts with VAMP2, the vesicular SNARE partner that is also present at high concentration in neuronal plasma membrane. This is the first report of VAMP2 interaction with an ion channel. The interaction was demonstrated in brain membranes and characterized using electrophysiological and biochemical analyses in Xenopus oocytes combined with an in vitro binding analysis and protein modeling. Comparative study performed with wild-type and mutant Kv2.1, wild-type Kv1.5, and chimeric Kv1.5N/Kv2.1 channels revealed that VAMP2 enhanced the inactivation of Kv2.1, but not of Kv1.5, via direct interaction with the T1 domain of the N terminus of Kv2.1. Given the proposed role for surface VAMP2 in the regulation of the vesicle cycle and the important role for the sustained Kv2.1 current in the regulation of dendritic calcium entry during high-frequency stimulation, the interaction of VAMP2 with Kv2.1 N terminus may contribute, alongside with the interaction of syntaxin with Kv2.1 C terminus, to the activity dependence of DCV release.     

Electrical remodelling maintains firing properties in cortical pyramidal neurons lacking KCND2-encoded A-type K+ currents

Considerable experimental evidence has accumulated demonstrating a role for voltage-gated K(+) (Kv) channel pore-forming (alpha) subunits of the Kv4 subfamily in the generation of fast transient outward K(+), I(A), channels. Immunohistochemical data suggest that I(A) channels in hippocampal and cortical pyramidal neurons reflect the expression of homomeric Kv4.2 channels. The experiments here were designed to define directly the role of Kv4.2 in the generation of I(A) in cortical pyramidal neurons and to determine the functional consequences of the targeted deletion of Kv4.2 on the resting and active membrane properties of these cells. Whole-cell voltage-clamp recordings, obtained from visual cortical pyramidal neurons isolated from mice in which the KCND2 (Kv4.2) locus was disrupted (Kv4.2-/- mice), revealed that I(A) is indeed eliminated. In addition, the densities of other Kv current components, specifically I(K) and I(ss), are increased significantly (P < 0.001) in most ( approximately 80%) Kv4.2-/- cells. The deletion of KCND2 (Kv4.2) and the elimination of I(A) is also accompanied by the loss of the Kv4 channel accessory protein KChIP3, suggesting that in the absence of Kv4.2, the KChIP3 protein is targeted for degradation. The expression levels of several Kv alpha subunits (Kv4.3, Kv1.4, Kv2.1, Kv2.2), however, are not measurably altered in Kv4.2-/- cortices. Although I(A) is eliminated in Kv4.2-/- pyramidal neurons, the mean +/- s.e.m. current threshold for action potential generation and the waveforms of action potentials are indistinguishable from those recorded from wild-type cells. Repetitive firing is also maintained in Kv4.2-/- cortical pyramidal neurons, suggesting that the increased densities of I(K) and I(ss) compensate for the in vivo loss of I(A).     

依普利酮部分逆转甲状腺激素诱导的心肌电重构

目的:研究醛固酮拮抗剂依普利酮对甲状腺激素(T3)诱导的心肌电重构的影响。方法:原代培养SD乳鼠心肌细胞,并随机分为对照组、T3组、依普利酮(Epl)组、T3+Epl组采用免疫荧光法鉴定心肌细胞,CCK-8法检测T3与依普利酮对心肌细胞存活率的影响,细胞免疫荧光法、real-time PCR法、Western blot法检测各组钾离子通道Kv1.5、Kv4.3,L型钙离子通道Cav1.2缝隙连接蛋白40(Cx40)和Cx43 mRNA与蛋白的表达。结果:免疫荧光法显示所培养细胞为心肌细胞且95%以上横纹肌α-辅肌动蛋白(sarcomericα-actinin,α-actinin)抗体染色阳性。与对照组比较,T3增加Kv1.5、Kv4.3、Cav1.2与Cx40 mRNA与蛋白的表达,减少Cx43 mRNA与蛋白的表达;Ep1组Kv1.5、Kv4.3、Cav1.2与Cx40 mRNA与蛋白的表达降低,Cx43的表达升高;与T3组比较,T3+Epl组Kv1.5、Kv4.3、Cav1.2与Cx40 mRNA与蛋白的表达降低,Cx43的表达升高。结论:依普利酮可部分逆转甲状腺激素导致的心肌电重构。