不同形态的家兔房室结细胞超极化钳制电流特性的研究

为探讨家兔房室结 3层细胞束细胞的电生理特性 ,按房室结 3层细胞束 4种细胞的形态特点 ,用胶原酶灌注分离房室结细胞并从中筛选 4种形态细胞 :圆形、椭圆形、细长形和条状形细胞 ,应用膜片钳全细胞记录技术观察各形房室结细胞超极化钳制电流的特征。超极化钳制时 ,房室结细胞中 12个条状形细胞中有 4个记录到较弱的内向整流钾电流 (Ik1 ) ,其他各形细胞均未记录到 Ik1 。大部分圆形和椭圆形细胞 (11 14 )记录到起搏电流 If,其电流密度为 - 4 .73± 0 .81p Ap F- 1 ,部分细长形细胞 (4 11)记录到较弱的 If,其电流密度为 - 0 .2 8± 0 .0 7p Ap F- 1 ,负向电流明显低于圆形和椭圆形细胞 (P<0 .0 1) ,长条形细胞除 1个外其余均未记录到 If。结果表明家兔房室结的 4种形态细胞的超极化钳制电流有明显不同 ,提示家兔房室结 3层细胞束的电生理及传导功能存在差异。     

Azimilide (NE-10064) Can Prolong or Shorten the Action Potential Duration in Canine Ventricular Myocytes:

Azimilide Effects on Membrane Voltage and Current. Introduction : Azimilide (NE-10064) has antiarrhythmic and antifibrillatory effects in canine models of ventricular arrhythmia. The goal of the present study was to examine the effects of azimilide on action potential and membrane currents of canine ventricular myocytes.
Methods and Results : Membrane voltage and current were recorded using the whole cell, patch clamp method. Azimilide at 1 /μM induced a consistent prolongation of action potential duration (APD): on average APD₉₀ was prolonged by 25% and 17% at stimulation rates of 0.33 and 1 Hz, respectively. Elevating the drug concentration to 5 μM induced APD prolongation in some cells but APD shortening in the others at 0.33 Hz, and a consistent APD shortening at 1 Hz. Azimilide suppressed the following currents (K_d in parenthesis): I_Kr (< 1 μM at -20 mV), I_Ks, (1.8 μM at +30 mV), L-type Ca current (17.8 μM at +10 mV), and Na current (19 μM at -40 mV). Azimilide was a weak blocker of the transient outward and inward rectifier currents (K_d≥ 50 μM at +50 and -140 mV, respectively). Azimilide blocked I_Kr, I_Ks, and I_Na in a use-dependent manner. Furthermore, azimilide reduced a slowly inactivating component of Na current that might be important for maintaining the action potential plateau in canine ventricular myocytes.
Conclusion : Azimilide has variable effects on APD in canine ventricular myocytes due to Us blocking effects on multiple currents with different potencies. Its Class III antiarrhythmic action is most likely seen at low concentrations (< 5 μM).     

Chromanol 293B inhibits slowly activating delayed rectifier and transient outward currents in canine left ventricular myocytes

INTRODUCTION: Drugs that selectively inhibit the slowly activating component of the delayed rectifier potassium current (I(Ks)) are being considered as possible antiarrhythmic agents, because they produce more prolongation of action potential duration at fast rates with less transmural dispersion of repolarization compared with blockers of the rapidly activating component (I(Kr)). Although the chromanol derivative chromanol 293B has been shown to be relatively selective in blocking I(Ks) in some species, its selectivity is far from established. METHODS AND RESULTS: The present study uses whole-cell, patch-clamp technique to examine the selectivity of this compound for inhibition of I(Ks) in comparison with other repolarizing ionic currents, such as I(Kr), inward rectifier potassium current (I(Kl)), transient outward current (I(to)), and L-type calcium current (I(Ca-L)) in canine left ventricular mid-myocardial and endocardial cells. Chromanol 293B blocked I(Ks) with an IC50 of 1.8 microM and I(to) with an IC50 of 38 microM. Concentrations as high as 30 microM did not affect I(Kl), I(Kr), or I(Ca-L). Higher concentrations of chromanol 293B (100 microM) caused a slight, but statistically insignificant, inhibition of I(Kr). CONCLUSION: Our results indicate that chromanol 293B is a relatively selective blocker of I(Ks) in canine left ventricular myocytes.     

Neurosteroids promote phosphorylation and membrane insertion of extrasynaptic GABAA receptors

Neurosteroids are synthesized within the brain and act as endogenous anxiolytic, anticonvulsant, hypnotic, and sedative agents, actions that are principally mediated via their ability to potentiate phasic and tonic inhibitory neurotransmission mediated by γ-aminobutyric acid type A receptors (GABA_ARs). Although neurosteroids are accepted allosteric modulators of GABA_ARs, here we reveal they exert sustained effects on GABAergic inhibition by selectively enhancing the trafficking of GABA_ARs that mediate tonic inhibition. We demonstrate that neurosteroids potentiate the protein kinase C-dependent phosphorylation of S443 within α4 subunits, a component of GABA_AR subtypes that mediate tonic inhibition in many brain regions. This process enhances insertion of α4 subunit-containing GABA_AR subtypes into the membrane, resulting in a selective and sustained elevation in the efficacy of tonic inhibition. Therefore, the ability of neurosteroids to modulate the phosphorylation and membrane insertion of α4 subunit-containing GABA_ARs may underlie the profound effects these endogenous signaling molecules have on neuronal excitability and behavior.Neurosteroids are synthesized de novo in the brain from cholesterol, or steroid hormone precursors. Raising neurosteroid levels in the CNS causes anxiolysis, sedation/hypnosis, anticonvulsant action, and anesthesia and reduces depressive-like behaviors (1–3). Accordingly, dysregulation of neurosteroid signaling is associated with premenstrual dysphoric disorder, panic disorder, depression, schizophrenia, and bipolar disorder. Neurosteroids exert the majority of their actions via potentiating the activity of γ-aminobutyric acid receptors (GABA_ARs), which mediate the majority of fast synaptic inhibition in the adult brain. Accordingly, at low nanomolar concentrations they potentiate GABA-dependent currents, whereas at micromolar concentrations they directly activate GABA_ARs (4–8).GABA_ARs are Cl⁻-preferring pentameric ligand-gated ion channels that assemble from eight families of subunits: α(1–6), β(1–3), γ(1–3), δ, ε, ө, π, and ρ(1–3) (9, 10). Receptor subtypes composed of α1–3βγ subunits largely mediate synaptic or phasic inhibition, whereas those constructed from α4–6β1–3, with or without γ/δ subunits, are principal determinants of tonic inhibition (11–13). Neurosteroids have been shown to bind GABA_ARs at an allosteric site distinct from that of GABA, benzodiazepines, or barbiturates (9, 14). Hosie et al. identified residues located within the transmembrane domain of GABA_AR α and β subunits that are critical for the direct activation (α1–6; Threonine 236, β1–3; Tyrosine 284) and allosteric potentiation (α1–6 Asparagine 407, and α1–6 Glutamine 246) of neurosteroids (15–17). Accordingly, mutation of glutamine 241 (Q241) within the α1–6 subunits prevents allosteric potentiation of GABA_AR composed of αβγ and αβδ subunits by neurosteroids (15, 16).In addition to modulating channel gating, neurosteroids exert potent effects on the expression levels of GABA_ARs (1, 18–20). Moreover, in the hippocampus, prolonged exposure to physiological concentrations of neurosteroids has been shown to enhance the tonic conductance mediated by extrasynaptic GABA_ARs containing the α4/δ subunits, while having little effect on the phasic conductance mediated by synaptic GABA_ARs (6, 21). However, the molecular mechanisms by which neurosteroids regulate GABA_AR expression levels remain unknown.Here, we reveal that neurosteroids act to increase the PKC-dependent phosphorylation of serine 443 (S443) within the intracellular domain of the α4 subunit. This process leads to increased insertion of α4 subunit-containing GABA_ARs into the plasma membrane and a selective enhancement of tonic inhibition. Thus, our experiments reveal a previously unidentified molecular mechanism by which neurosteroids exert sustained effects on GABAergic inhibition by selectively increasing α4-containing GABA_ARs in the membrane and therefore potentiate tonic inhibition.     

Effects of combined radiofrequency and direct current energy catheter ablation on ventricular myocardium in pigs

When radiofrequency catheter ablation of ventricular arrhythmiasis unsuccessful, an option may be to combine it with directcurrent energy. We therefore investigated the effects of sucha combination. Radiofrequency energy was delivered in a bipolar or unipolarfashion to the left and right ventricles through an ablationcatheter with a tip electrode 2 mm long, using a temperature-guidedradiofrequency generator. Radiofrequency ablation was followedby a single cathodal direct current shock (66 J) with the ablationcatheter positioned similarly in six closed-chest pigs. In acontrol group (six animals) only direct current ablation wasperformed, with one or two energy applications (66 J) in eachventricle. Two of six animals in the radiofrequency I direct current groupdied due to perforation in the follow-up period, 1 and 3.5 hafter the direct current ablation, respectively. Gross pathologicalexamination of the hearts revealed transmural lesions in allanimals. In the radiofrequency I direct current group four lesionswere perforated, three of which were located in the left ventricle.There was a significant increase in the number of perforationsin the radiofrequency/direct current group compared to the controlgroup, where perforation was never observed Haemorrhagic pericardialfluid was found in five of the six animals in the radiofrequency/directcurrent group compared to none in the control group. These findings show that myocardial ablation with radiofrequencyenergy followed by direct current energy in the same sessionmay have a high complication rate.     

采用膜片钳技术记录心室肌细胞离子流

本文报告了心室肌细胞分离方法,采用膜片钳技术,成功地记录了细胞膜钾、钙、钠离子流,初步显示背景钾离子通道活性的电压依赖性,钙、钠离子通道活性为电压和时间依赖性,钠离子通道开放速率最快,电压在-30mV。钠离子流达峰电流仅需1ms,其活性也表现电压和时间依赖性。     

甲状腺素诱发大鼠心肌肥厚时瞬时外向钾电流、内向整流钾电流和钙电流的变化

目的 研究甲状腺素诱发大鼠心肌肥厚模型的心肌细瞬时外向钾电流、内向整流钾电流和钙电流的变化。方法 以ipL-甲门面腺素造成大鼠心肌肥厚模型后,用膜片钳技术记录心肌细胞瞬时外向钾电流、内向整流钾电流和L型钙电流。结果 肥厚组心肌细胞瞬时外向钾电流幅度和心坎产增加,激活动力学特性无改变;内向整流钾电流幅度和密度也增加,激活动力学特性也无改变;而钙电流幅度、细胞膜电容增加,电流密度不变,半数激活电压（V1/2）向负电位方向移动,斜率（k)减小。结论 在甲状腺素诱发大鼠心肌肥厚模型中瞬时外向钾电流、内向整流钾电流和钙电流特性均发生了变化,这是造成肥厚心肌电生理异常的离子基础。     

心肌细胞晚钠离子流与心血管疾病

近年来的研究证明,心肌细胞膜钠通道晚钠离子流(晚/Na)与心血管疾病,尤其与缺血性心脏病及其相关疾病状态的发生、发展密切相关。晚/Na抑制剂雷诺嗪能有效抑制晚/Na内流,进而缓解心肌缺血,改善心脏舒缩功能和遏止相关心律失常的发生。目前为止,除众多基础研究的证据外,尚有雷诺嗪治疗慢性缺血性心脏病临床试验的证据。现就晚/Na与缺血性心脏病及其相关疾病,如稳定型心绞痛、心功能不全和心律失常的关系及雷诺嗪心血管保护作用的研究进展做一综述。     

小檗碱衍生物CPU86035对豚鼠心室肌钾离子通道的影响

目的观察小檗碱衍生物溴苄基四氢小檗碱(CPU86035)对豚鼠心室肌细胞钾离子流的影响,探讨其抗心律失常的离子通道机制。方法20只健康豚鼠,雌雄不拘,体重250-300 g,双酶法酶解获取单个豚鼠心室肌细胞,采取用药前后自身对照及全细胞膜片钳记录方法观察CPU86035 对正常豚鼠心室肌细胞快速激活延迟整流钾离子流(IKr)和缓慢激活延迟整流钾离子流(IKs)、内向整流钾离子流(IK1)的影响。结果CPU86035对豚鼠单个心室肌细胞快速激活(IKr)和缓慢激活延迟整流钾离子流(IKs)均呈浓度依赖性抑制作用,半数抑制浓度(ID50)分别为32μM和56 μM;CPU86035 对Ix1无明显影响。结论CPU86035对正常豚鼠心室肌细胞快速激活延迟整流钾离子流(Ikr)和缓慢激活延迟整流钾离子流(IKs)均有阻断作用,具有复合Ⅲ类抗心律失常药物的特点。     

Resveratrol Attenuates Ventricular Arrhythmias and Improves the Long-Term Survival in Rats with Myocardial Infarction

Objective  The effects of resveratrol treatment on ventricular arrhythmia, survival, and late cardiac remodeling were evaluated in rats with myocardial infarction (MI). Methods  Three groups of rats (sham-operated, MI, and MI pre-treated with resveratrol) were treated in an in vivo MI model by ligation of left anterior descending coronary artery. The electrocardiogram signals were monitored and recorded for 24 h using an implanted telemetry transmitter. The incidence of ventricular arrhythmias during the first 24-h after MI was also evaluated. Meanwhile, invasive in vivo electrophysiology with pacing in the right ventricle was performed in each group to assess the inducibility of ventricular arrhythmias. Results  Administration of resveratrol significantly suppressed the MI-induced ventricular tachycardia and ventricular fibrillation (0.4 ± 0.2 in Resv group vs. 7.1 ± 2.2 in MI group episodes per hour per rat, P < 0.01). Data also showed that the incidence of inducible ventricular tachycardia was lower in the Resv group than the MI group (46% vs. 81%, P < 0.01). The infarct size and mortality in the Resv group at 14 weeks were reduced by 20% and 33%, respectively, compared with the MI groups. Results from patch clamp recording revealed that resveratrol inhibited L-type calcium current (I _Ca-L), and selectively enhanced ATP-sensitive K⁺ current (I _K,ATP) in a concentration-dependent manner. Conclusion  These results suggested that the emerging anti-arrhythmic character induced by resveratrol treatment in rat hearts could be mainly accounted for by inhibition of I _Ca-L and enhancement of I _K,ATP. Administration of resveratrol also improved the long-term survival by suppressing left ventricular remodeling. You-Ren Chen and Fang-Fang Yi contributed equally to this work.     

西洛他唑对大鼠右心室肌细胞离子通道的影响

目的：观察西洛他唑对大鼠右心室肌细胞离子通道的影响,探讨西洛他唑预防Brugada综合征室性心律失常发生的离子通道机制。
　　方法：本研究包括两部分实验：①灌流实验,分为1、2、5、50μmol/L西洛他唑组,每组记录的细胞数分别为9、5、3、7个。分别观察每组给药前后瞬间外向钾电流（Ito）电流密度的变化,并观察四组间用药前后Ito电流密度变化的差异;②口服药物实验,分为空白1组、实验1组、空白2组、实验2组,每组选用的大鼠数分别为7、5、8、6只,分别观察实验组与空白组Ito、L-型钙电流（ICa,L）电流密度的差异。
　　结果：灌流实验结果：①在1、2、5、50μmol/L西洛他唑各组中,细胞灌流药物后Ito电流密度均降低,在自指令电压+60 mV时,各组用药前后的Ito电流密度差异有统计学意义（P均＜0.05）。②在各指令电压下时,不同浓度西洛他唑灌流液灌流细胞后Ito电流密度减少率,四组间差异均无统计学意义（P均>0.05）。口服药物实验结果：①在自指令电压-50 mV到最大+60 mV,实验1组Ito电流密度较空白1组无明显变化,差异无统计学意义（P>0.05）;②在自指令电压为+10 mV,空白2组ICa,L电流密度较实验2组略高,但差异无统计学意义（P>0.05）。
　　结论：1、2、5、50μmol/L西洛他唑灌流液直接作用于大鼠右心室肌细胞,均能明显的抑制Ito,但西洛他唑1~50μmol/L范围内对Ito的抑制程度没有差异。西洛他唑可能具有抑制Brugada综合征心律失常发生的作用。     

The ionic mechanisms of long QT interval in diabetic rabbits

Objective Abnormal QT prolongation associated with arrhythmias is considered the major cardiac electrical disorder and a significant predictor of mortality in diabetic patients. The precise ionic mechanisms for diabetic QT prolongation remained unclear. The present study was designed to analyze the changes of ventricular repolarization and the underlying ionic mechanisms in diabetic rabbit hearts. Methods Diabetes was induced by a single injection ofalloxan （145mg/kg, Lv. ）. After the development of diabetes （10 weeks）, ECG was measured. Whole-cell patch-clamp technique was applied to record the action potential duration （APD50, APD90）, slowly activating outward rectifying potassium current （IKs）, L-type calcium current （ICa-L） and inward rectifying potassium current （IK1）. Results The action potential duration （APD50 and APD90） of ventricular myocytes was obviously prolonged from 271.5＋32.3 ms and 347.8＋36.3 ms to 556.6~72.5 ms and 647.9~72.2 ms respectively （P〈 0.05）. Meanwhile the normalized peak current densities of IKs in ventricular myocytes investigated by whole-cell patch clamp was smaller in diabetic rabbits than that in control group at test potential of＋50mV （1.27~0.20 pA/pF vs 3.08~0.67 pA/pF, P〈0.05）. And the density of the ICa-L was increased apparently at the test potential of 10 mV （-2.67~0.41 pA/pF vs -5.404-1.08 pA/pF, P〈0.05）. Conclusion Ventricular repolarization was prolonged in diabetic rabbits, it may be partly due to the increased L-type calcium current and reduced slow delayed rectifier K＋ current （IKs） （J Geriatr Cardio12010; 7：25-29）.     

Calmodulin and the philosopher's stone: Changing Ca2+ into arrhythmias

Calmodulin and the Philosopher's Stone. It has been recognized for some time that intracellular Ca2+ ([Ca2+]i) can contribute to the genesis of cardiac arrhythmias, but understanding of the molecular signaling machinery that links disordered [Ca2+]i to arrhythmias has been lacking. Exciting recent work has focused on the ubiquitous intracellular Ca2+-binding protein calmodulin. Calmodulin is a molecular sensor that can translate increases in [Ca2+]i into modulatory signals for ion channels and activate other Ca2+-dependent signaling molecules. This article will examine the implications of these recent findings for arrhythmogenesis and the development of new antiarrhythmic therapies.     

Comparison of the effects of a transient outward potassium channel activator on currents recorded from atrial and ventricular cardiomyocytes

Effect of NS5806 on Atrial Currents. Introduction: NS5806 activates the transient outward potassium current (I_to) in canine ventricular cells. We compared the effects of NS5806 on canine atrial versus ventricular tissues and myocytes. Methods and Results: NS5806 (10 μM) was evaluated in arterially perfused canine right atrial and right ventricular wedge preparations. In ventricular wedges NS5806 (10 μM) accentuated phase 1 in epicardium (Epi), with little effect in endocardium (Endo), resulting in augmented J‐waves on the ECG. In contrast, application of NS5806 (10 μM) to atrial preparations had no effect on phase 1 repolarization but significantly decreased upstroke velocity (dV/dt) and depressed excitability, consistent with sodium channel block. Current and voltage‐clamp recordings were made in the absence and presence of NS5806 in (10 μM) enzymatically dissociated atrial and ventricular myocytes. In ventricular myocytes, NS5806 increased I_to magnitude by 80% and 16% in Epi and Endo, respectively (at +40 mV). In atrial myocytes, NS5806 increased peak I_to by 25% and had no effect on the sustained current, I_Kur. Under control conditions, I_Na density in atrial myocytes was nearly double that in ventricular myocytes. NS5806 caused a shift in steady‐state mid‐inactivation (V_1/2) from –73.9 ± 0.27 to –77.3 ± 0.21 mV in ventricular and from –82.6 ± 0.12 to –85.1 ± 0.11 mV in atrial cells, resulting in reduction of I_Na in both cell types. Expression of mRNA encoding putative I_Na and I_to channel subunits was evaluated by qPCR. Conclusion: NS5806 produces a prominent augmentation of I_to with little effect on I_Na in the ventricles, but a potent inhibition of I_Na with little augmentation of I_to in atria. (J Cardiovasc Electrophysiol, Vol. 22, pp. 1057‐1066, September 2011)     

Kv1.4通道电流与大鼠心室肌细胞瞬间外向钾电流特性的比较

克隆的大鼠外向钾通道Ｋｖ１．４亚型表达于２９３细胞（ＲＣＫ４）。用膜片钳全细胞钳制法系统比较该克隆的大鼠瞬间外向钾电流（Ｉｔｏ）和天然大鼠心室肌细胞Ｉｔｏ的特点和动力学特性。两种通道电流形态相似,呈“Ａ”型电流,在＋４０ｍＶ时电流失活时间常数τ依次为３６．６±２ｍｓ和４１．０±２ｍｓ（Ｐ＞０．０５）。Ｋｖ１．４通道电流激活曲线用二相Ｂｏｌｔｚｍａｎｎ方程拟合,一相半数最大激活电位（Ｖ１／２,１）为－２１．０±３．９ｍＶ、二相半数最大激活电位（Ｖ１／２,２）为２７．０±３．９ｍＶ;天然大鼠心室肌细胞Ｉｔｏ激活曲线用单相Ｂｏｌｔｚｍａｎｎ方程拟合,半数最大激活电位为１０．８±１．１ｍＶ（Ｐ＜０．０５,ｖｓＫｖ１．４通道电流的Ｖ１／２,１）。ＲＣＫ４细胞通道电流半数最大灭活电位（Ｖ１／２）为－４９．８±１．８ｍＶ,斜率因子（ｋ）为３．８±０．２７;天然大鼠心室肌细胞Ｉｔｏ的Ｖ１／２为－３１．６±１．７ｍＶ,ｋ为５．４±０．２１。灭活后再激活的恢复时间比较,Ｋｖ１．４通道电流明显长于天然大鼠心室肌细胞Ｉｔｏ,分别为１．８９±０．２ｓ和３９．２±１．６ｍｓ（Ｐ＜０．０５）。研究表明克隆的大鼠Ｋｖ１．４通道电流与天然大?     

小儿心导管射频消融术的麻醉体会

射频消融术是治疗快速性心律失常安全、有效的方法。本文报导42例小儿心导管射频消融术的麻醉处理，认为咪唑安定和芬太尼静脉复合麻醉具有安全、起效快、麻醉过程平稳、深度适宜、无明显副作用的特点，对手术过程无明显影响，是射频消融术一种安全、可行的麻醉方法。     

黄连素对大鼠结肠上皮隐窝细胞基底膜钾通道的影响

目的研究黄连素对结肠上皮隐窝细胞基底膜钙依赖钾通道[IK（Ca）]和环磷酸腺苷（cAMP）依赖钾通道[IK（cAMP）]的影响，探讨其治疗分泌性腹泻的机制。方法用乙二胺四乙酸（EDTA）溶液分离结肠上皮隐窝细胞，运用EPC10膜片钳放大器测量全细胞模式下50、100、500μmol／L黄连素对结肠上皮细胞基底膜IK（Ca）和IK（cAMP）的影响，并设PSS对照组。结果50、100、500μmol／L黄连素可抑制大鼠结肠上皮隐窝细胞基底膜IK（Ca）和IK（cAMP）（P值均〈0．05），当阶跃刺激为＋80mV时，其IK（Ca）分别为对照组的（71．43±3．61）％、（54．56±5．13）％、（38．66±3．85）％（P〈0．05）；其IK（cAMP）分别为对照组的（78．55±5．72）％、（60．42±6．33）％、（43．78±6．47）％（P〈0．05）。结论黄连素能抑制大鼠结肠上皮细胞基底膜IK（Ca）和IK（cAMP）的开放，这可能是其治疗分泌性腹泻的机制之一。     

低强度自主神经节刺激对犬心房离子电流的影响

目的 研究6h低强度自主神经节(GP)刺激对犬乙酰胆碱依赖性钾电流(IKACh)和L型钙电流(ICaL)的影响.方法 22只成年杂种犬随机分为2组:实验组16只,对左上GP及右前GP予以6h低强度高频刺激;对照组6只,在心房远离GP处同样予以6h低强度刺激.刺激结束后分别用膜片钳、实时定量反转录-聚合酶链反应( RT-PCR)和蛋白免疫印迹(Western Blot)技术检测右心房(RA)、左心房(LA)及左上肺静脉(LSPV)处组织IKACh和ICaL密度,以及相应通道亚单位Kir 3.4和CaV 1.2的mRNA水平和蛋白含量水平.结果 与对照组相比,6h低强度高频刺激可以导致:①LSPV处IKACh电流密度[ (9.8±0.6) pA/pF对(7.9±0.3)pA/pF,P＜0.01]和相应的通道亚单位Kir 3.4蛋白水平(3.3±0.5对1.6±0.1,P＜0.001)显著增加;②RA、LA及LSPV处ICaL电流密度[RA:(2.0±0.2) pA/pF对(2.8±0.2) pA/pF,P＜0.01;LA:(2.3±0.3) pA/pF对(5.0±0.3) pA/pF,P＜0.001; LSPV:(2.5±0.2) pA/pF对(4.3±0.4)pA/pF,P＜0.01]和相应的通道亚单位CaV 1.2蛋白水平(RA:0.8±0.1对1.1±0.1,P＜0.01;LA:1.1±0.1对1.7±0.2,P＜0.01;LSPV:0.5±0.1对0.8±0.1,P＜0.001)显著下降;③Kir 3.4(RA:0.9±0.1对0.8±0.1,P＞0.05;LA:1.0±0.1对0.9±0.1,P＞0.05;LSPV:1.1±0.1对1.1 ±0.0,P＞0.05)和CaV 1.2(RA:0.9±0.1对1.0±0.1,P＞0.05;LA:0.8±0.1对0.9±0.1,P＞0.05;LSPV:1.1±0.1对1.1±0.1,P＞0.05)的mRNA水平差异无统计学意义.结论 6h低强度GP刺激可以通过转录后调节引起IKACh电流密度增加和ICaL电流密度的下降.     

Altered transient outward current in human atrial myocytes of patients with reduced left ventricular function

INTRODUCTION: Electrophysiologic remodeling is involved in the self-perpetuation of atrial fibrillation. To define whether differences in atrial electrophysiology already are present in patients with increased susceptibility for atrial fibrillation, we compared patients in sinus rhythm with and without heart failure. METHODS AND RESULTS: Atrial specimens were obtained from patients with reduced left ventricular ejection fraction (LVEF; n = 10) and normal LVEF (n = 16) who were undergoing aortocoronary bypass surgery and from donor hearts (n = 4). Enzymatically isolated atrial myocytes were investigated by whole cell, patch clamp techniques. Total outward current was significantly larger in myocytes of hearts with low LVEF than normal LVEF (19.4 +/- 1.3 vs 15.1 +/- 1.2 pA/pF at pulses to +60 mV, respectively). Analysis of inactivation time courses of different outward current components revealed that the observed current difference is due to the transient calcium-independent outward current I(to1) which is twice as large in the low LVEF group than in the normal LVEF group (9.4 +/- 0.9 vs 4.7 +/- 0.4 pA/pF at pulses to +60 mV, respectively). I(to1) recovery from inactivation was significantly more rapid in myocytes of hearts with low LVEF, and action potential plateau in these cells was significantly shorter. The results of I(to1) and action potential measurements in atrial myocytes of donor hearts were very similar to the results of patients with preserved heart function. CONCLUSION: I(to1) in human atrial myocytes of patients with reduced LVEF has an increased density and altered kinetics in sinus rhythm. These differences in outward current may explain the reduced plateau phase of action potentials.