腺苷对心房肌细胞钾钙通道的影响及受体机制

运用膜片钳全细胞记录方式，研究腺苷（Ａｄｏ）及选择性腺苷Ａ１受体阻滞剂８－环戊基－１，３－二丙基黄嘌呤（ＤＰＣＰＸ）对豚鼠心房肌细胞延迟整流性钾通道电流（ＩＫ）和Ｌ－型钙通道电流（Ｌ－ＩＣａ）的影响及受体机制。结果表明：３μｍｏｌ／Ｌ Ａｄｏ可加强ＩＫ，其峰值电流增大（Ｐ〈０．０１），ＩＫ尾电流Ｉｋ．ｔａｉｌ亦增大，Ｉｋ．ｔａｉｌ的快、慢失活时间常数均减少。同时Ａｄｏ可抑制Ｌ－ＩＣａ，峰值电流减少     

成年小鼠心房肌细胞分离方法的改进及钾电流记录

目的建立稳定、重复性好的小鼠心房肌细胞分离技术,观察小鼠心房肌细胞形态以及钾通道电流特性,为进一步研究小鼠心房肌细胞的电生理特性打下基础。方法在体视显微镜下行主动脉插管,应用Langendorff装置恒流灌流,依次用无钙台氏液、酶消化液(含Ⅱ型胶原酶和胰蛋白酶)灌流,灌流完成后,剪除心室组织,心房组织块用消化酶液(仅含Ⅱ型胶原酶)行二步消化,分离出小鼠单个心房肌细胞,采用标准的全细胞膜片钳技术记录动作电位和钾电流,电流的电压-电流曲线(I-V曲线)以电压为横坐标,每个电压值下的电流密度(pA/pF)为纵坐标拟合而成。结果本法分离所得小鼠心房肌细胞呈长梭形、横纹清晰,细胞耐钙,具有正常电生理活性,细胞贴壁好,从而易于形成高阻封接;记录小鼠心房肌细胞动作电位为近似于三角形,静息电位为(-70.2±4.9)mV;记录的瞬时外向钾电流(Ito)激活非常快,达峰值后快速失活,峰电流存在明显的电压依赖性和外向整流特征,电流峰值为(11.1±1.9)pA/pF;超速激活的延迟整流钾电流(IKur)激活迅速,几乎无延迟现象,失活缓慢,峰电流呈现出外向整流特征,该电流约在-20 mV被激活,峰电流存在明显的电压依赖性,峰值(7.0±1.5)pA/pF。内向整流钾电流(IK1)随着超极化刺激电位的增加,电流密度增加,在-140 mV时,其内向电流的峰值为(27.0±2.3)pA/pF。结论此方法可成功获取适合做膜片钳实验的单个小鼠心房肌细胞,操作方法简便,可行性高,重复性好。     

氨茶碱对大鼠膈肌细胞L型钙通道的影响

目的:研究氨茶碱对大鼠膈肌细胞L型钙通道的电生理作用。方法:采用全细胞膜片钳（whole cell patchclamp）技术,当维持电位为-80mv,刺激频率为0.5Hz,钳制时间为300ms,步进电压为10mv,去极到60mv,观察氨茶碱对膈肌细胞L型钙通道（L-ICa）的影响。结果:氨茶碱用药后大鼠膈肌细胞平均内向峰值L型钙电流为（-6.5±0.5）pA/pF;正常未用药组为（-5.6±0.5）pA/pF,其增加的幅度为14.6±2.5％,两组比较差异有显著性（P<0.01）。结论:氨茶碱可激活膈肌细胞膜的钙通道,增加Ca2+内流,而使膈肌细胞的收缩力增强,为临床治疗膈肌疲劳提供理论依据。     

治疗浓度的雷诺嗪对人心房肌细胞电活动的影响

目的:探讨治疗浓度的雷诺嗪对人心房肌细胞电活动的影响。方法:从冠状动脉旁路移植术患者右心耳分离心房肌细胞,在治疗浓度的雷诺嗪作用下,使用膜片钳技术记录动作电位(APD)及峰钠电流、L型钙通道电流(LCa,L)、瞬时外向钾电流(Ito)、超快速延迟整流钾电流(IKur),观察给药前后的变化。结果:10μmol/L雷诺嗪使APD50和APD90分别延长27.5%和14.2%,而对静息电位和动作电位的幅度无明显影响;使钠电流失活曲线V0.5从(-92.9±7.8)mV左移至(-103.5±3.9)mV,对ICa,L、Ito、IKur的电流-电压曲线无明显影响。结论:10μmol/L雷诺嗪延长APD50和APD90,并使快钠通道失活增加。     

花生四烯酸对L-型钙通道的作用及其抗心律失常机制

目的 研究花生四烯酸(arachidonic acid,AA)对家兔单个心室肌细胞L-广型钙通道的作用及其抗心律失常作用的机制.方法 采用酶解法分离得到家兔单个心室肌细胞,全细胞膜片钳技术记录单个心室肌细胞L-型钙电流(L-type calcium current,Ica-L),用累积给药的方法在灌流液中加入不同浓度的AA,观察给药前后L-型钙电流的变化,统计学方法采用单因素方差分析.结果 不同浓度的从均能明显抑制心室肌细胞,Ica-L.3 μmol/L,μmol/L,20,μmol/L的AA使Ica-L峰电流密度从(10.79±0.93)pA/pF分别减少剑(8.99 ±0.43)pA/pF、(7.60 ±0.35)pA/pF和(5.60±0.30)pA/pF(n=7,P<0.05),经冲洗后Ica-L可部分恢复,并且AA可使Ica-L的I-V关系曲线上移,其形状和峰值电压保持不变;20 μmol/L的AA使Ica-L失活曲线左移,失活后恢复时间明显延长,但对激活曲线无明显影响.结论 花生四烯酸可通过加快L-型钙通道失活,延长其失活后的恢复过程而减少细胞外钙离子的内流,延长有效不应期,从而发挥抗心律失常作用.     

复方鳖甲软肝方对家兔心室肌细胞钙通道的影响

目的研究复方鳖甲软肝方对家兔单个心室肌细胞L-型钙通道(ICa-L)的电生理作用.方法采用改良的中药血清药理学方法及全细胞膜片钳技术观察不同浓度的复方鳖甲软肝方药物血清干预心肌细胞后对心肌细胞ICa-L电流的影响.结果含0.7 g/L和1.4 g/L的复方鳖甲软肝方药物血清使兔心室肌细胞ICa-L峰值电流密度(ICa-L max)由(6.90±0.52)pA/pF分别下降至(3.40±0.28)pA/pF和(2.30±0.18)pA/pF(P＜0.01).复方鳖甲软肝方使ICa-L的电流-电压曲线上移,但不改变其激活电位、电位峰值和反转电位,同时还抑制ICa-L的激活过程.结论复方鳖甲软肝方对ICa-L具有浓度依赖性阻滞作用,这可能是其抗心肌纤维化的部分机制.     

增龄犬左心房肌细胞动作电位和L型钙通道的变化

背景：增龄是心房颤动发生的独立危险因素,心房肌细胞电生理特性的变化是触发和维持心房颤动的重要因素。目的：观察不同年龄犬左心房肌细胞动作电位和L型钙通道的改变。方法：实验纳入7只成年犬和10只老年犬,用Ⅱ型胶原酶分离成年犬和老年犬的左心房肌细胞,用全细胞膜片钳方法记录成年犬和老年犬左心房肌细胞动作电位和L型钙通道电流;采用实时荧光定量PCR和Western blot检测左心房肌L型钙通道α1c亚基mRNA和蛋白的表达。结果与结论：与成年犬相比,老年犬左心房肌细胞动作电位平台期的幅度明显降低（P〈0.05）,动作电位时程明显延长（P〈0.05）,而最大舒张电位和动作电位幅度在老年犬和成年犬间差异无显著性意义（P〉0.05）;同时老年犬左心房肌细胞的L型钙通道电流密度较成年犬明显降低（P〈0.05）,而L型钙通道电流动力学参数在成年犬和老年犬间差异无显著性意义（P〉0.05）;此外,与成年犬相比,老年犬左心房肌L型钙通道α1c亚基mRNA和蛋白的表达明显降低（P〈0.05）。由此认为,左心房肌细胞电生理学特性存在增龄性改变。     

CCK—8可对抗μ—阿片受体介导的对大鼠背根节神经元钙通道的？…

ＣＣＫ－８在脊髓水平可对抗μ－阿片受介导的抗伤害性作用，但其作用位点及机制尚不清楚。本实验以急性分离的大鼠背根节（ＤＲＧ）神经地为根本，用全细胞膜片钳（ｗｈｏｌｅ－ｃｅｌｌ ｐａｔｃｈ－ｃｌａｍｐ）方法记录钙通道电流，观察分析特异性μ－受体激动剂羟甲芬太尼（ＯＭＦ）对电压依赖性钙通道电流的作用，以及在同一细胞上ＣＣＫ－８对此作用的影响。结果显示ＯＭＦ可明显抑制钙通道电流，其抑制作用可被μ－受体拮抗     

参麦注射液和氨茶碱对大鼠膈肌细胞L型钙通道的影响

目的 :研究参麦注射液和氨茶碱对大鼠膈肌细胞L型钙通道 (L LCa)的影响。方法 :采用急性酶解法获得大鼠单个膈肌细胞。在保持电位为 - 80mv ,去极化到 6 0mv ,波宽为 30 0ms的刺激参数下 ,用标准的全细胞膜片钳技术记录L型钙通道 ,观察参麦注射液 (SMI)、氨茶碱对其的影响。结果 :5 0 μl/ml的参麦注射液、10 -4 mol/L的氨茶碱分别使大鼠膈肌细胞平均内向峰值L型钙电流由 (- 6 .9± 0 .6 )pA/ pF(n =7)增加到 (- 8.4± 0 .6 ) pA/pF和(- 7.9± 0 .5 ) pA/pF ,其增加的幅度为 (2 2 .14± 1.7) %、(14.6± 2 .5 ) % ,两组比较差异均有显著性 (P <0 .0 5 )。结论 :参麦注射液和氨茶碱均可激活膈肌细胞膜的钙通道 ,增加Ca2 内流 ,而使膈肌细胞的收缩力增强 ,该作用可能是其在临床上用于治疗膈肌疲劳的离子通道机制之一     

CCK－8可对抗μ－阿片受体介导的对大鼠背根节神经元钙通道的抑制效应

ＣＣＫ－８在脊髓水平可对抗μ－阿片受体介导的抗伤害性作用，但其作用位，点及机制尚不清楚。本实验以急性分离的大鼠背根节（ＤＲＧ）神经元为标本，用全细胞膜片钳（ｗｈｏｌｅ－ｃｅｌｌｐａｔｃｈ－ｃｌａｍｐ）方法记录钙通道电流，观察分析特异性μ－受体激动剂羟甲芬太尼（ＯＭＦ）对电压依赖性钙通道电流的作用，以及在同一细胞上ＣＣＫ－８对此作用的影响。结果显示ＯＭＦ可明显抑制钙通道电流，其抑制作用可被μ－受体拮抗剂纳络酮或ＣＣＫ－８所翻转，而ＣＣＫ－８的作用又可被ＣＣＫ－Ｂ受体拮抗剂Ｌ３６５，２６０所对抗。结果提示：ＣＣＫ－８可在同一细胞上经ＣＣＫ－Ｂ受体对抗阿片效应。ＣＣＫ－８本身对钙通道电流并无增强效应，相反它可引起抑制作用。关于ＣＣＫ－８如何对抗μ－受体介导的机制有待进一步研究。     

Inhibition of G protein-coupled and ATP-sensitive potassium currents by 2-methyl-3-(3,5-diiodo-4-carboxymethoxybenzyl)benzofuran (KB130015), an amiodarone derivative

2-Methyl-3- (3,5-diiodo-4-carboxymethoxybenzyl) benzofuran (KB130015; KB), a novel compound derived from amiodarone, has been proposed to have antiarrhythmic properties. Its effect on the G protein-coupled inward rectifying K+ current [IK(ACh) or IK(Ado)], ATP-sensitive K+ current [IK(ATP)], and background inward rectifying current (I(K1)) were studied in guinea pig atrial and ventricular myocytes by the whole-cell voltage-clamp technique. Receptor-activated IK(ACh/Ado), induced in atrial myocytes by the stimulation of either muscarinic or Ado receptors was concentration dependently (IC50 value of approximately 0.6-0.8 microM) inhibited by KB. Receptor-independent guanosine 5'-O-(3-thio)triphosphate-induced and background IK(ACh), which contributes to the resting conductance of atrial myocytes, were equally sensitive to KB (IC50 value of approximately 0.9 microM). IK(ATP) induced in atrial myocytes during metabolic inhibition with 2,4-dinitrophenol (DNP) was also suppressed by KB, whereas IK1 measured in ventricular myocytes was insensitive to the drug (KB < or =50 microM). Although being effective when applied from the outside, intracellular application of KB via the patch pipette affected neither IK(ACh) nor IK(ATP). 3,3',5-triodo-L-thyronin, which shares structural groups with KB, did not have an effect on the K+ currents. Consistent with the effects on single myocytes, KB did not depolarize the resting potential but antagonized the shortening of action potential duration by carbamylcholine-chloride or by DNP in multicellular preparations and antagonized the shortening of action potential duration by acetylcholine in single myocytes. It is concluded that KB inhibits IK(ACh) and IK(ATP) by direct drug-channel interaction at a site more easily accessible from extracellular side of the membrane.     

腺苷对不同部位心肌细胞的电生理作用比较

运用标准玻璃微电极技术记录豚鼠心房肌、心室肌及房室结区细胞动作电位．比较和研究腺苷对它们的电生理作用。结果表明．腺苷可明显缩短心房肌细胞AP房室结区细胞的APD．并降低房室结区细胞APA及Vmax．而对心室肌细胞AP各参数无影响。其作用可被选择性A1受体拮抗剂DPCPX所消除．本文同时还探讨了踪着对不同部位心肌细胞产生不同效应的可能机制。     

Effect of ambasilide, a new class III agent, on plateau currents in isolated guinea pig ventricular myocytes: block of delayed outward potassium current.

The actions of ambasilide (LU-47110) on the action potential and membrane currents of isolated guinea pig ventricular myocytes were studied using voltage clamp techniques. Ambasilide (1 microM) prolonged the action potential (APD) at 20, 50 and 90% repolarization by 11.2 +/- 4.3, 13.8 +/- 3.9 and 13.6 +/- 3.7%, respectively, compared to control (n = 10). APD prolongation was attributed to the block of delayed rectifier outward current (Ik) in a concentration-dependent fashion (0.01-10 microM). The effects on the APD and Ik were both partially reversed after perfusion with drug-free Tyrode's solution. The block of Ik by ambasilide was compared to that by E-4031 (5 microM), a putative selective blocker of that fast, inwardly rectifying component of Ik identified in guinea pig ventricle. E-4031 produced about 65% block of Ik for pulse durations between 80 and 420 msec, but the block decreased as the pulse duration increased further, the block accounting for 34 +/- 5% of Ik at 6.3 sec. In contrast, the percentage of reduction of Ik by 10 microM ambasilide did not produce a consistent magnitude of block over a similar range of short depolarizations, but rather progressively decreased Ik as the pusle duration lengthened. Block at the end of a 2-sec pulse was about 48 +/- 8%, more block than could be attributed to an E-4031-sensitive current block alone. Whereas E-4031 (5 microM) shifted the activation curve of Ik 10 mV toward positive potentials and decreased the slope factor, k, by about 4 mV, ambasilide (5 microM) had no effect on these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)     

血管紧张素Ⅱ及卡托普利对犬心房肌细胞外向钾通道电流的作用

目的 观察血管紧张素Ⅱ(AngⅡ)及卡托普利对犬心房肌细胞外向钾通道电流的作用,揭示其参与房性心律失常的细胞电生理机制.方法 健康成年杂种犬(普通级)10只,体质量(15-20)k,雌椎不拘,天津利群实验动物服务中心提供.急性分离单个犬心房肌细胞,采用伞细胞膜片钳方法 分别记录Ang Ⅱ及卡托普利灌流前后细胞膜快速延迟整流钾电流(Ikr)、缓慢延迟整流钾电流(Ikr)、超快速延迟整流钾电流(Ikr)及短暂外向钾电流(It0).采用pClamp 7.0 for windows及pClampfit7.0软件测量电流;数据用均数±标准差((-x)±s)表爪;应用SPSS 10.0统计软件进行统汁学分析,用药前后的比较采用自身配财t枪验,以P<0.05为差异有统计学意义.结果 0.5t mol/L Ang Ⅱ可增加,Ikr、Iks,抑制Ito[(19.54±2.41)pA/pF VS.(24.83±2.52)pA/pF,P=0.001;(20.69 4±2.29)pA/pF vs.(25.59±3.42)pA/pF,P=0.0003;(6.34±1.93)pA/pF vs.(3.71±1.50)pAZpF,P=0.001)],对Ikur无明显影响[(19.78±1.22)pA/pF vs.(20.39±1.50)pA/pF,P=0.258];5 mol/L卡托普利对,¨Iks Ikur 及均无明显作用[(19.11±4.91)pA/pF vs.(18.99±4.04)pA/pF,P=O.808;(20.76±2.89)pA/pF vs.(20.27±3.46)pA/pF,P=0.305;(18.50±3.78)pA/pF VS.(18.25±4.02)pA/pF,P=0.704;(7.31±1.99)pA/pF vs.(6.89±2.12)pA/pF,P=0.136)].结论 Ang II通过对外向钾电流的影响促进心房颤动时的心房屯重构,卡托普利作为血管紧张素转换酶抑制剂,可能通过抑制肾素.血管紧张素系统呆改善心房颤动时的心房电重构,对心房颤动有防治作用.     

Natriuretic and vasodilating activities of intrarenally administered atriopeptin II, substance P and bradykinin in the dog

The mechanism of the diuretic effect of atrial natriuretic factor is unclear. In this study, we compared the renal vasodilating and diuretic effects of renal arterial infusions of rat atriopeptin II in anesthetized dogs to see if natriuresis and increases in total renal blood flow were associated. The vasodilators substance P and bradykinin also were tested. Volume (V), Na+ and K+ concentration and Na+ and K+ content (UNaV; UkV) of urine from the infused and contralateral kidneys (IK; CK) were measured as well as mean total renal blood flow (RBF) of the IK. Atriopeptin II (30-1000 ng/kg/min) slightly promoted RBF by up to 20%, but raised V, UNaV and UkV by a maximum of 79, 190 and 100%, respectively. Substance P (0.01-30 ng/kg/min) raised RBF of IK by a maximum of 59%, reduced mean blood pressure by 26% and had a biphasic effect on IK excretion: V, UNaV and UkV were increased maximally by 105, 154 and 42% at 1.0 ng/kg/min, whereas progressively less diuresis, natriuresis and kaliuresis occurred at higher (hypotensive) doses. CK excretion was unchanged. Bradykinin (1-100 ng/kg/min) raised RBF, V, UNaV, and UkV of IKs by a mean maximum of 97, 70, 201 and 47%, respectively, with no changes in mean blood pressure or CK excretion. The natriuretic and hyperemic effects of nonhypotensive doses of each peptide were significantly correlated. However, atriopeptin II uniquely promoted Na+ excretion, but not RBF at the lowest dose tested, and, after 10 min washout of the 1000-ng/kg/min dose, and did not appreciably promote RBF after 10 min of infusion. It also caused CK diuresis.(ABSTRACT TRUNCATED AT 250 WORDS)     

自然杀伤T淋巴细胞对黑色素瘤细胞的免疫调节及杀伤功能实验研究

目的探讨自然杀伤T淋巴细胞(NKT细胞)在细胞免疫调节及杀伤功能中的作用。方法建立混合淋巴细胞培养(MLC)体系,B16F10-luc-G5细胞作为靶细胞,以总淋巴细胞为效应细胞。(1)调节效应实验以NKT细胞或CD4~+CD25~+T淋巴细胞为调节细胞,分为3组:NKT组、CD4~+CD25~+T组、靶细胞空白对照组;另设有1640空白对照组(RPMI1640溶液)。(2)杀伤效应实验以NKT或自然杀伤(NK)细胞为效应细胞,分为3组:NKT组、NK组、靶细胞空白对照组。混合培养24、48、72h后,通过活体成像系统检测该培养系统的靶细胞生物发光,以监测NKT细胞的调节及杀伤效应。结果 (1)调节效应实验:NKT组及CD4~+CD25~+T组测定光子数分别与两空白对照组比较,以及NKT组内培养24h与72h时测得光子数比较,差异均有统计学意义(P0.05)。(2)杀伤效应实验:NKT组及NK组与靶细胞空白对照组所测光子数比较,差异均有统计学意义(P0.05);且培养24、72h时NKT组与NK组光子数比较,差异均有统计学意义(P0.05)。结论 NKT细胞具有抑制总淋巴细胞对靶细胞的杀伤效应,且抑制效应具有时间性,其调节作用较CD4~+CD25~+T淋巴细胞强。NKT细胞具有对靶细胞的杀伤效应,但较NK细胞弱。     

Change of Atrial Refractory Period after Short Duration of Rapid Atrial Pacing: Regional Differences and Possible Mechanisms

It is unknown whether there are regional differences in the cimnge of atrial effective refractory period (EBP) after a short duration of rapid atriai pacing. Furthermore, the effects of calcium channel and potassium channel on this phenomenon have not been extensively investigated. In opened-chest dogs, the endocardial monophasic action potential duration at 90% repolarization (APD₉₀) from the right atrial appendage, and ERP from seven atrial sites were measured before and after rapid atrial pacing at 800 beats/min for 30 minutes. Both atrial ERP and APD₉₀ significantly shortened after rapid atrial pacing. The postpacing atria EBP and APD₉₀ shortening persisted for 1.19 ± 3 and 123 ± 4 seconds after cessation of pacing, respectively. There was no significant difference in the magnitude or recovery course of atrial ERP shortening after pacing among the seven atrial sites. Pretreatment with nicorandil and d-sotalol had no effects on the magnitude or recovery course of atrial EBP shortening after pacing. However, the degree of ERP and APD₉₀shortening after pacing was significantly atten uated in the verapamil and ryanodine groups; furthermore, the recovery of ERP and APD₉₀ after cessation of pacing was faster in the two groups. In conclusion, shortening of atrial EBP induced by short-duration rapid atrial pacing was uniform in both atria. Both the adenosine triphosphatase (ATP) dependent potassium current and rapid component of the delayed rectifier did not significantly influence this phenomenon, but both the verapamil and ryanodine could significantly attenuate the degree of atrial ERP and APD₉₀ shortening.     

Tedisamil blocks the transient and delayed rectifier K+ currents in mammalian cardiac and glial cells

The potassium currents in rat and guinea pig ventricular myocytes and mouse astrocytes were studied using tedisamil, a novel antiarrhythmic agent. A 1 to 20 microM dosage of tedisamil caused marked prolongation of the action potential in isolated rat ventricular myocytes, mimicking its reported effects on multicellular rat heart preparations. Under voltage clamp conditions, tedisamil caused a dose-dependent increase in the speed of inactivation of the transient outward K+ current (Ito), the predominant outward current in rat ventricular myocytes. In cardiac myocytes, the tedisamil block was neither use- nor voltage-dependent. The slow reversibility of drug action when applied from the outside, and its effectiveness when applied intracellularly, suggested an internal site of drug action. In guinea pig ventricular myocytes, tedisamil blocked the slowly developing time-dependent delayed rectifier K+ current (IK) over the same concentration range as that found for Ito in the rat myocytes. Tedisamil reduced this current without changing the characteristics of its slow (tau approximately 1 sec) activation. The effects of tedisamil on Ito and IK were independent of the phosphorylation state of the channel, as assessed by the equal effectiveness of the drug in the presence or absence of isoproterenol. Tedisamil also blocked the transient K+ current and the delayed rectifier current (IK) in mouse astrocytes over the same concentration range as that found in the cardiac myocytes and by a process that accelerated (transient K+ current) or mimicked (IK) inactivation. At concentrations of up to 50 microM, tedisamil had little effect on the time-dependent inward rectifier K+ current, or inward calcium current in rat or guinea pig ventricular myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronotropic and inotropic effects of terikalant on isolated, blood-perfused atrial and ventricular preparations of dogs

Summary— We investigated the effects of terikalant, which blocks inward rectifier K⁺ current, on the sinus rate, atrial and ventricular contractile force in the isolated, blood-perfused right atrial and left ventricular preparations of dogs, and the effects of terikalant on the negative cardiac responses to acetylcholine, adenosine or pinacidil (an ATP-sensitive K⁺ channel opener) and on the positive cardiac responses to norepinephrine. Terikalant (1–100 nmol) decreased sinus rate and briefly and slightly increased atrial contractile force in isolated atria. However, terikalant did not increase ventricular contractile force in isolated ventricles. Neither propranolol nor atropine inhibited the positive inotropic and negative chronotropic responses to terikalant, respectively. Terikalant (10 or 30 nmol) did not significantly affect the negative cardiac responses to acetylcholine, adenosine nor pinacidil and the positive responses to norepinephrine. These results suggest that terikalant decreases sinus rate with a small changes in myocardial contractile force and does not affect the cardiac responses to muscarinic and adenosine receptor agonists, ATP-sensitive K⁺ channel openers nor β-adrenoceptor agonists in the dog heart.     

Clinical characteristics and treatment of short QT syndrome

Short QT syndrome is a new inherited disorder associated with familial atrial fibrillation and/or sudden death or syncope. To date, three different mutations in genes encoding cardiac ion channels (KCNH2, KCNQ1 and KCNJ2) have been identified as causing short QT syndrome. All mutations lead to a gain in function of the affected current (IK(r), IK(s )and IK(1)). The syndrome is characterized in the few patients identified so far by a shortened QT interval of less than 300-325 ms after correction for heart rate at rates below 80 beats per minute. However, no boundary or limit for the QT interval can yet be determined, as more knowledge about this disease is still restricted to a small patient population. Furthermore, the QT interval lacks adaptation to heart rate. The majority of patients exhibit shortened atrial and ventricular effective refractory periods and inducibility of ventricular fibrillation. Death already occurs in newborns, so the short QT syndrome may also account for deaths classified as sudden infant death syndrome. The therapy of choice in families with a history of sudden death or syncope seems to be the implantable cardioverter-defibrillator. Whether patients without a family history of sudden death or symptoms need a defibrillator cannot yet be answered, and requires further investigation. Pharmacologic treatment has only been investigated in patients with a mutation in KCNH2 (HERG), and it could be demonstrated that the mutant currents may be insufficiently suppressed by drugs that are targeted to block the specific current (e.g., sotalol or ibutilide) in patients with a mutation in the IK(r-)coding gene KCNH2 (HERG). Interestingly, in this specific patient population, quinidine proved to be efficient in prolonging the QT interval and normalizing the effective refractory periods. Implantable cardioverter-defibrillator therapy is associated with an increased risk of inappropriate therapies for T-wave oversensing, although this risk can be resolved by reprogramming implantable cardioverter-defibrillator detection algorithms.