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研究生:陳亞妤
研究生(外文):Chen ya-yu
論文名稱:心基因缺陷小鼠心室肌細胞激發性以及自動性節律之探討
論文名稱(外文):Study on Triggered and Automatic Rhythms of Ventricular Myocytes Obtained from Xin Deficient Mouse Hearts
指導教授:林正一林正一引用關係
指導教授(外文):Lin Cheng-I
學位類別:碩士
校院名稱:國防醫學院
系所名稱:生理學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2006
畢業學年度:94
語文別:中文
論文頁數:61
中文關鍵詞:心基因介間盤心律不整
外文關鍵詞:Xin geneintercalated discarrhythmias
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中文摘要
前言:
心臟動作電位的發生和傳導與離子通道的活性、細胞與細胞間的傳導和心臟組織的結構有著複雜的關聯。近年來學者研究指出,Xin是一個Nkx2.5轉錄因子的下游基因,可能參與對心臟發育相當重要的BMP-Nkx2.5-MEF2C途徑。利用雙標記免疫螢光染色法 (double–label immunofluorescent ),發現Xin蛋白在胚胎時期即與β-catenin、N–cadherin有90﹪的重疊,在成鼠心臟介間盤的部分,Xin蛋白亦和connexin 43有80﹪重疊,顯示Xin蛋白表現於介間盤(intercalated disc)的adheren junction,在gap junction也可能有表現。因此心基因不僅對於心臟分化發育相當重要,對於心肌細胞間的連結、衝動傳導以及細胞骨架間的整合也扮演關鍵角色。因此心基因缺陷,可能造成介間盤結構缺損或是細胞間傳導障礙,相關研究亦顯示心基因缺陷小鼠會產生心肌肥大的現象。

實驗目的:
比較野生型小鼠(wild–type mice)與心基因缺陷小鼠 (Xin–deficient
mice;Xin+/- and Xin-/-) 之心室肌細胞動作電位、激發性心律不整和不正常
自動性節律發生機率,以及相關離子電流的表現,以利探討心基因陷缺小
鼠是否比較容易引發心律不整。
實驗方法:
一、 Xin基因型小鼠的鑑定
本實驗取小鼠尾巴做聚合酵素連鎖反應 (polymerase chain reaction, PCR),以確定實驗用的每隻小鼠之基因型態。
二、小鼠心室肌細胞之分離
1. 將10–20週小鼠(體重為20–30公克)以sodium pentobarbital (50 mg/Kg i.p.)麻醉,經胸腔部開術取心臟出置於HEPES– Tyrode溶液中。
2. 以絲線將主動脈口固定於0.35 mm PE管的一端,另一端則與Langendorff灌流柱接合,以37℃ 100% 氧氣飽和灌流液進行冠狀動脈逆行性灌流,將心臟內之血液灌洗出,直至血液完全排出。
3. 以Ca2+–free HEPES– Tyrode溶液灌洗4–6分鐘,目的使心臟不再跳動、組織完全鬆弛。
4. 以Ca2+–free HEPES– Tyrode溶液含有collagenase (1 mg/ml)及protease(0.01 mg/ml)等兩酵素進行酵素溶液灌流,灌流約2–6分鐘不等。
5. 最後以Ca2+–free HEPES– Tyrode溶液灌洗10分鐘,減少酵素作用。分離出單一細胞後,逐次以HEPES–Tyrode溶液將Ca2+–free HEPES–Tyrode溶液更換掉,將鈣離子濃度回昇至生理常態濃度。

三、單一心室肌細胞之電生理研究
本實驗採whole–cell patch–clamp 方法,以電位箝定觀察三種型態小
鼠之心室肌細胞各離子電流的變化;及電流箝定觀察動作電位之異
同。
四、實驗數據分析:利用unpair t-test、One-way ANOVA以及卡方檢定
(Chi-square)進行數據分析。

實驗結果:
一、 以實驗中記錄到的細胞電容,比較心基因缺陷小鼠與野生型小鼠心室肌細胞大小差異,結果野生型小鼠、心基因缺陷小鼠異質體及同質體細之胞電容依序為101.3±5.8 pF、104±6.6 pF、132.4±7.8 pF,同質體小鼠無論是和異質體或是野生型小鼠比較,結果顯示均達統計顯著差異。表示此時期心基因同質體缺陷小鼠之心室肌細胞有明顯肥大的情形。
二、 在電流箝定模式下1Hz的電刺激誘發動作電位。三組間比較,心基因缺陷小鼠再極化50﹪、90﹪的動作電位期間(APD50、APD90)與野生型小鼠比較皆有顯著延長。APD50:依序為9.4±0.5 ms、20.5±5.5 ms及16.7±2.9 ms;APD90:依序為96.2±10 ms、138.6±17.0 ms及127.7±9.9 ms。
三、 三組在電流箝定模式下,1 Hz的電刺激下皆可記錄到EAD(early after-depolarization)、DAD(delayed after-depolarization)以及自動性節律的情形。其中EAD發生的機率,心基因同質體缺陷小鼠(26/44)較野生型小鼠(7/24)高,且達統計顯著差異。
四、 電位箝定下,發現心基因同質體缺陷小鼠INa (sodium current)在-40 mV(-7.7±1.6 pA/pF比上-3.2±0.9 pA/pF)、-30 mV(-9.2±1.5 pA/pF比上-3.9±2.5 pA/pF)電流密度較野生型小鼠大。Iti(transient inward current)之電流密度亦較野生型小鼠大(0.6±0.1 pA/pF比上0.4±0.1 pA/pF);順向INCX電流密度較小,且達統計顯著差異。而T型鈣離子流(ICa,T)則是三組皆無表現。

結論:
此心基因缺陷動物模式除了在心臟傳導可提供臨床相關研究,在心臟肥大、心律不整方面與其離子電流的改變,亦可提供臨床治療方針的參考。
ABSTRACT

Introduction
Xin, one of the downstream targets of the Nkx2.5 and MEF2C transcription factors, is a striated muscle-specific gene. Xin protein localizes to the adherens junctions and gap junctions of the intercalated discs. It may play important roles in cardiac morphogenesis, formation and maintenance of the intercalated disc and myofibril integrity. Xin may also participate in generation and propagation of cardiac action potential. Xin expression is significantly up-regulated in pressure-overload animals and deficiency of Xin may lead to spontaneous hypertrophy in the hearts.

Aim
The aims of the present study were to compare the action potential characteristics, triggered and automatic rhythms and the ionic remodeling of Xin-deficient ventricular myocytes with wild-type ventricular myocytes.

Material and Methods
a. Gene typing
PCR(polymerase chain reaction)was used to confirm genomic type of Xin-deficient mice.
b. Isolation of ventricular myocytes
Male mice (C57BL/6J, 20–30 gm) and age–matched male Xin-deficient mice (20–30 gm) were anesthetized with sodium pentobarbital (50mg/Kg i.p.) and the heart and lungs quickly removed and immersed in Tyrode solution. The heart was perfused in a retrograde manner via polyethylene tube connected to the aorta. The free end of the polyethylene tubing was connected to a Langendorff perfusion column for perfusion with normal Tyrode’s solution at 37 ℃. The perfusion was replaced with oxygenated Ca2+–free Tyrode’s solution, then was replaced with solution containing collagenase (1 mg/ml) and protease (0.01 mg/ml) finally. Afterwards, the ventricle was cut away from the atrium and lung and placed in a dissection chamber containing Ca2+–free oxygenated Tyrode’s solution. The piece of tissue was cut into fine pieces and shaken in 20 ml of oxygenated Ca2+–free Tyrode solution until single ventricular myocytes obtained.
c. Electrophysiological study
The isolated cells were placed in a chamber mounted on the stage of an inverted microscope and superfused with extracellular solution appropriate to each patch–clamp experiment. Only cells showing clear cross striations were used for experiment on following ion currents and membrane potentials by means of whole–cell patch–clamp technique.
We respectively used current-clamp and voltage-clamp mode to record action potential characteristics and ionic currents, including ICa,T, INa, INCX and Iti.
d. Statistical analysis:
One-way ANOVA, unpair t-test and Chi-square were used to analyze data.

Results
The presented study showed that:
(1) The membrane capacitance(Cm)of Xin-deficient ventricular myocytes was significantly larger than wild-type ones, which proved that Xin-deficient animal could exhibit cardiac hypertrophy.
(2) The current density of INa and Iti in Xin-deficient ventricular myocytes were significantly increased, and the current density of forward mode Ni2+-sensitive INCX was reduced as compared to that of
wild-type ventricular myocytes. ICa,T was absent among three groups.
(3) As to the action potential characteristics, we found out that action potential duration was significantly prolonged and the incidence of early after-depolarization(EAD) was significantly higher in Xin-deficient ventricular myocytes. However, the incidence of delayed after-depolarization(DAD)and automatic rhythms had no significant difference among three groups.

Conclusion
The Xin-deficient mice might be an ideal animal model for structure-related electrophysiological study on the genesis of cardiac arrhythmias in cardiac hypertrophy.
目錄
頁次
目錄------------------------------------------------------------------------------I
圖目錄--------------------------------------------------------------------------IV
表目錄--------------------------------------------------------------------------V
中文摘要-----------------------------------------------------------------------VI
英文摘要-----------------------------------------------------------------------X
第一章 緒言------------------------------------------------------------1
第一節 介間盤(intercalated disk)簡介-------------------------1
第二節 心基因 (Xin–gene) 簡介-----------------------------------2
第三節 不正常自發性節律以及激發性節律的介紹------------5
第四節 和動作電位相關的離子流簡介---------------------------7
第二章 研究目的-----------------------------------------------------11
第三章 材料與方法--------------------------------------------------12
第一節 實驗動物-----------------------------------------------------12
第二節 小鼠心室肌細胞之分離-----------------------------------12
第三節 玻璃微電極與實驗裝置-----------------------------------14
第四節 全細胞膜電位箝定-----------------------------------------14
第五節 電生理實驗方法--------------------------------------------16
第六節 實驗藥物及溶液--------------------------------------------17
第七節 鑑定小鼠的Xin基因型-----------------------------------19
第八節 實驗數據與統計--------------------------------------------23
第四章 實驗結果--------------------------------------------------------24
第一節 鑑定小鼠的Xin基因型-----------------------------------24
第二節 野生型小鼠與心基因缺陷小鼠之心室肌細胞動作電位
比較-----------------------------------------------------------24
第三節 野生型小鼠與心基因缺陷小鼠之心室肌細胞各離子電
流比較 ------------------------------------------------------27


第五章 討論------------------------------------------------------------38
第一節 心基因缺陷導致心肌肥大之探討---------------------39
第二節 心基因缺陷與野生型小鼠動作電位方面之探討
---------------------------------------------------------------40
第三節 心基因缺陷與野生型小鼠心室肌細胞鈉離子電流
之探討-----------------------------------------------------41
第四節 心基因缺陷與野生型小鼠心室肌細胞的鈉鈣交換
離子電流之探討------------------------------------------42
第五節 心基因缺陷與野生型小鼠心室肌細胞T型鈣離子
流之探討--------------------------------------------------44
第六節 心基因缺陷與野生型小鼠心室肌細胞的短暫內向
離子電流與激發性心律不整之探討------------------46
第七節 對心基因缺陷小鼠心室肌細胞離子電流特性研究之總結
---------------------------------------------------------------48
第六章 結論--------------------------------------------------------------49
第七章 參考文獻--------------------------------------------------------51

圖目錄
圖1 心臟 發育及其相關的基因流程示意圖--------------------------10
圖4–1 鑑定Xin基因型小鼠的聚合酵素連鎖反應 (PCR)圖-----30
圖4–2 電刺激下,小鼠心室肌細胞之典型動作電位圖-----------32
圖4–3 電刺激下,小鼠心室肌細胞記錄到的激發性心律不整-33
圖4–4 小鼠心室肌細胞鈉離子流之比較圖--------------------------34
圖4–5 小鼠心室肌細胞納鈣交換離子流之比較圖-----------------35
圖4–6 小鼠心室肌細胞T型與L型鈣離子電流之比較圖-------36
圖4–7 小鼠心室肌細胞短暫內向離子電流之比較圖--------------37


表目錄
表一 小鼠之心室肌細胞的動作電位參數比較----------------------31
第七章 參考文獻

1.Ahmmed GU, Dong PH, Song G, Ball NA, Xu Y, Walsh RA, and Chiamvimonvat N:Changes in Ca2+ cycling proteins underlie cardiac action potential prolongation in a pressure-overloaded guinea pig model with cardiac hypertrophy and failure. Circ Res 86: 558-570, 2000.
2.Armoundas AA, Hobai IA, Tomaselli GF, Winslow RL, and O'Rourke B:Role of sodium-calcium exchanger in modulating the action potential of ventricular myocytes from normal and failing hearts. Circ Res 93: 46-53, 2003.
3.Bers DM:Cardiac excitation-contraction coupling. Nature 415: 198-205, 2002.
4.Chen YJ, CS, Yeh HI , Chang MS and Lin CI:Electrophysiology of single cardiomyocytes isolated from rabbit pulmonary veins: implication in initiation of focal atrial fibrillation. Basic Res Cardiol 97: 26-34, 2002.
5.Cheng CP, Loh YX, Lai YJ, Chen YC, H.K. and Lin CI in:Electrophysiological Characteristics of Ventricular Myocytes Obtained from Xin Deficient Mouse Hearts. MSc.thesis. NDMC, 2005.
6.Cheng CP, Loh YX, Lin CI , Lai YJ , Chen YC, Sytwu HK , Gustafson-Wagner EA and Lin J.J-C:Electrophysiological characteristics of ventricular myocytes of Xinα-deficient mice. in: Advances in Heart Disease-Proceedings of the 12th World Congress on Heart Disease. New Trends in Reasearch, Diagnosis and Treatment., edited by Asher Kimchi, Medimond,srl, Bologna, Italy, 2006, pp.25-30.
7.Cherepanova O, Orlova A, Galkin VE, van der Ven PF, Furst DO, Jin JP, and Egelman EH:Xin-repeats and nebulin-like repeats bind to F-actin in a similar manner. J Mol Biol 356: 714-723, 2006.
8.Cribbs LL, Martin BL, Schroder EA, Keller BB, Delisle BP, and Satin J: Identification of the T-type calcium channel (Ca(v)3.1d) in developing mouse heart. Circ Res 88: 403-407, 2001.
9.Danik SB, Liu F, Zhang J, Suk HJ, Morley GE, Fishman GI, and Gutstein DE:Modulation of cardiac gap junction expression and arrhythmic susceptibility. Circ Res 95: 1035-1041, 2004.
10.Despa S, Islam MA, Weber CR, Pogwizd SM, and Bers DM:Intracellular Na+ concentration is elevated in heart failure but Na/K pump function is unchanged. Circulation 105: 2543-2548, 2002.
11.Droogmans G and Nilius B:Kinetic properties of the cardiac T-type calcium channel in the guinea-pig. J Physiol 419: 627-650, 1989.
12.Dupont E, Matsushita T, Kaba RA, Vozzi C, Coppen SR, Khan N, Kaprielian R, Yacoub MH, and Severs NJ:Altered connexin expression in human congestive heart failure. J Mol Cell Cardiol 33: 359-371, 2001.
13.Gilmour RF and Zipes DP:Afterdepolarizations, triggered rhythms and cardiac arrhythmias. in Molecular Physiology and Pharmacology of Cardiac Ion Channel and Transporters.edited by Morad M., Ebashi S., Trautwein W., and Kurachi Y., Kluwer Academic Pub., Dordrecht, Boston, 1996, pp.333-342.
14.Glasser SP:The relevance of T-type calcium antagonists: a profile of mibefradil. J Clin Pharmacol 38: 659-669, 1998.
15.Go A, Srivastava S, Collis L, Coetzee WA, and Artman M:Negative inotropic effect of nifedipine in the immature rabbit heart is due to shortening of the action potential. Pediatr Res 57: 399-403, 2005.
16.Gray RP, McIntyre H, Sheridan DS, and Fry CH.:Intracellular sodium and contractile function in hypertrophied human and guinea-pig myocardium. Pflugers Arch 442: 117-123, 2001.
17.Hasenfuss G, Reinecke H, Studer R, Meyer M, Pieske B, Holtz J, Holubarsch C, Posival H, Just H, and Drexler H:Relation between myocardial function and expression of sarcoplasmic reticulum Ca2+-ATPase in failing and nonfailing human myocardium. Circ Res 75: 434-442, 1994.
18.Henderson SA, Goldhaber JI, So JM, Han T, Motter C, Ngo A, Chantawansri C, Ritter MR, Friedlander M, Nicoll DA, Frank JS, Jordan MC, Roos KP, Ross RS, and Philipson KD:Functional adult myocardium in the absence of Na+-Ca2+ exchange: cardiac-specific knockout of NCX1. Circ Res 95: 604-611, 2004.
19.Hilgemann DW, Matsuoka S, Nagel GA, and Collins A:Steady-state and dynamic properties of cardiac sodium-calcium exchange. Sodium-dependent inactivation. J Gen Physiol 100: 905-932, 1992.
20.Houser SR, Piacentino V, 3rd, and Weisser J:Abnormalities of calcium cycling in the hypertrophied and failing heart. J Mol Cell Cardiol 32: 1595-1607, 2000.
21.Jinglin Zeng YR:Early afterdepolarizations in cardiac myocytes: mechanism and rate dependence. Biophys J 68: 949-964, 1995.
22.Kaab S, Dixon J, Duc J, Ashen D, Nabauer M, Beuckelmann DJ, Steinbeck G, McKinnon D, and Tomaselli GF:Molecular basis of transient outward potassium current downregulation in human heart failure: a decrease in Kv4.3 mRNA correlates with a reduction in current density. Circulation 98: 1383-1393, 1998.
23.Kaab S, Nuss HB, Chiamvimonvat N, O'Rourke B, Pak PH, Kass DA, Marban E, and Tomaselli GF:Ionic mechanism of action potential prolongation in ventricular myocytes from dogs with pacing-induced heart failure. Circ Res 78: 262-273, 1996.
24.Kaprielian R, Wickenden AD, Kassiri Z, Parker TG, Liu PP, and Backx PH:Relationship between K+ channel down-regulation and [Ca2+]i in rat ventricular myocytes following myocardial infarction. J Physiol 517 ( Pt 1): 229-245, 1999.
25.Kiss E, Ball NA, Kranias EG, and Walsh RA:Differential changes in cardiac phospholamban and sarcoplasmic reticular Ca2+-ATPase protein levels. Effects on Ca2+ transport and mechanics in compensated pressure-overload hypertrophy and congestive heart failure. Circ Res 77: 759-764, 1995.
26.Kostetskii I, Li J, Xiong Y, Zhou R, Ferrari VA, Patel VV, Molkentin JD, and Radice GL:Induced deletion of the N-cadherin gene in the heart leads to dissolution of the intercalated disc structure. Circ Res 96: 346-354, 2005.
27.Kostin S, Hein S, Arnon E, Scholz D, and Schaper J:The cytoskeleton and related proteins in the human failing heart. Heart Fail Rev 5: 271-280, 2000.
28.Kuo HC, Cheng CF, Clark RB, Lin JJ, Lin JL, Hoshijima M, Nguyen-Tran VT, Gu Y, Ikeda Y, Chu PH, Ross J, Giles WR, and Chien KR:A defect in the Kv channel-interacting protein 2 (KChIP2) gene leads to a complete loss of Ito and confers susceptibility to ventricular tachycardia. Cell 107: 801-813, 2001.
29.Lebeche D, Kaprielian R, and Hajjar R:Modulation of action potential duration on myocyte hypertrophic pathways. J Mol Cell Cardiol 40: 725-735, 2006.
30.Li J, Patel VV, Kostetskii I, Xiong Y, Chu AF, Jacobson JT, Yu C, Morley GE, Molkentin JD, and Radice GL:Cardiac-specific loss of N-cadherin leads to alteration in connexins with conduction slowing and arrhythmogenesis. Circ Res 97: 474-481, 2005.
31.Lin J.J-C, Gustafson-Wagner EA, Sinn HW , Choi SJ, Jaacks SM, Wang DZ , Evans S. , and Lin J. L-C:Structure, expression, and function of a novel intercalated disc protein, Xin. J Med Sci 25: 215-222, 2005.
32.Luo CH and Rudy Y:A dynamic model of the cardiac ventricular action potential. II. Afterdepolarizations, triggered activity, and potentiation. Circ Res 74: 1097-1113, 1994.
33.Lyons I, Parsons LM, Hartley L, Li R, Andrews JE, Robb L, and Harvey RP:Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeo box gene Nkx2-5. Genes Dev 9: 1654-1666, 1995.
34.Matsushita T, Oyamada M, Fujimoto K, Yasuda Y, Masuda S, Wada Y, Oka T, and Takamatsu T:Remodeling of cell-cell and cell-extracellular matrix interactions at the border zone of rat myocardial infarcts. Circ Res 85: 1046-1055, 1999.
35.McKoy G, Protonotarios N, Crosby A, Tsatsopoulou A, Anastasakis A, Coonar A, Norman M, Baboonian C, Jeffery S, and McKenna WJ:Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease). Lancet 355: 2119-2124, 2000.
36.McNair WP, Ku L, Taylor MR, Fain PR, Dao D, Wolfel E, and Mestroni L: SCN5A mutation associated with dilated cardiomyopathy, conduction disorder, and arrhythmia. Circulation 110: 2163-2167, 2004.
37.Meszaros J, Khananshvili D, and Hart G:Mechanisms underlying delayed afterdepolarizations in hypertrophied left ventricular myocytes of rats. Am J Physiol Heart Circ Physiol 281: H903-914, 2001.
38.Mitra R and Morad M:Two types of calcium channels in guinea pig ventricular myocytes. Proc Natl Acad Sci U S A 83: 5340-5344, 1986.
39.Nabauer M, Beuckelmann DJ, and Erdmann E:Characteristics of transient outward current in human ventricular myocytes from patients with terminal heart failure. Circ Res 73: 386-394, 1993.
40.Nuss HB and Houser SR:T-type Ca2+ current is expressed in hypertrophied adult feline left ventricular myocytes. Circ Res 73: 777-782, 1993.
41.Pacholsky D, Vakeel P, Himmel M, Lowe T, Stradal T, Rottner K, Furst DO, and van der Ven PF:Xin repeats define a novel actin-binding motif. J Cell Sci 117: 5257-5268, 2004.
42.Papadatos GA, Wallerstein PM, Head CE, Ratcliff R, Brady PA, Benndorf K, Saumarez RC, Trezise AE, Huang CL, Vandenberg JI, Colledge WH, and Grace AA: Slowed conduction and ventricular tachycardia after targeted disruption of the cardiac sodium channel gene Scn5a. Proc Natl Acad Sci U S A 99: 6210-6215, 2002.
43.Pashmforoush M, Lu JT, Chen H, Amand TS, Kondo R, Pradervand S, Evans SM, Clark B, Feramisco JR, Giles W, Ho SY, Benson DW, Silberbach M, Shou W, and Chien KR:Nkx2-5 pathways and congenital heart disease; loss of ventricular myocyte lineage specification leads to progressive cardiomyopathy and complete heart block. Cell 117: 373-386, 2004.
44.Perriard JC, Hirschy A, and Ehler E:Dilated cardiomyopathy: a disease of the intercalated disc? Trends Cardiovasc Med 13: 30-38, 2003.
45.Peters NS, Green CR, Poole-Wilson PA, and Severs NJ:Reduced content of connexin43 gap junctions in ventricular myocardium from hypertrophied and ischemic human hearts. Circulation 88: 864-875, 1993.
46.Pogwizd SM and Bers DM:Cellular basis of triggered arrhythmias in heart failure. Trends Cardiovasc Med 14: 61-66, 2004.
47.Pogwizd SM, Qi M, Yuan W, Samarel AM, and Bers DM:Upregulation of Na+/Ca2+ exchanger expression and function in an arrhythmogenic rabbit model of heart failure. Circ Res 85: 1009-1019, 1999.
48.Pogwizd SM, Schlotthauer K, Li L, Yuan W, and Bers DM:Arrhythmogenesis and contractile dysfunction in heart failure: Roles of sodium-calcium exchange, inward rectifier potassium current, and residual beta-adrenergic responsiveness. Circ Res 88: 1159-1167, 2001.
49.Pogwizd SM, Sipido KR, Verdonck F, and Bers DM:Intracellular Na in animal models of hypertrophy and heart failure: contractile function and arrhythmogenesis. Cardiovasc Res 57: 887-896, 2003.
50.Reuter H, Pott C, Goldhaber JI, Henderson SA, Philipson KD, and Schwinger RH:Na+--Ca2+ exchange in the regulation of cardiac excitation-contraction coupling. Cardiovasc Res 67: 198-207, 2005.
51.Schaper J, Froede R, Hein S, Buck A, Hashizume H, Speiser B, Friedl A, and Bleese N:Impairment of the myocardial ultrastructure and changes of the cytoskeleton in dilated cardiomyopathy. Circulation 83: 504-514, 1991.
52.Schott JJ, Benson DW, Basson CT, Pease W, Silberbach GM, Moak JP, Maron BJ, Seidman CE, and Seidman JG:Congenital heart disease caused by mutations in the transcription factor NKX2-5. Science 281: 108-111, 1998.
53.Schultheiss TM, Burch JB, and Lassar AB:A role for bone morphogenetic proteins in the induction of cardiac myogenesis. Genes Dev 11: 451-462, 1997.
54.Schwinger RH, Bohm M, Schmidt U, Karczewski P, Bavendiek U, Flesch M, Krause EG, and Erdmann E:Unchanged protein levels of SERCA II and phospholamban but reduced Ca2+ uptake and Ca2+-ATPase activity of cardiac sarcoplasmic reticulum from dilated cardiomyopathy patients compared with patients with nonfailing hearts. Circulation 92: 3220-3228, 1995.
55.Sinn HW, Balsamo J, Lilien J, and Lin JJ:Localization of the novel Xin protein to the adherens junction complex in cardiac and skeletal muscle during development. Dev Dyn 225: 1-13, 2002.
56.Swynghedauw B, Levy B, Tedgui A, Sanders MR, Kostis JB, Ostadl B, Kolar F, Schunkert H, Riegger GAJ, Malliani A, Benlian P and Young P:Ion basis of resting and action potential. in : Cardiac Cellular Electrophysiology. edited by Carmeliet E, Vereecke J, Kluwer Academic Publishers, Boston, 2002, pp.95-178
57.Tomaselli GF and Marban E:Electrophysiological remodeling in hypertrophy and heart failure. Cardiovasc Res 42: 270-283, 1999.
58.Triggle DJ:The physiological and pharmacological significance of cardiovascular T-type, voltage-gated calcium channels. Am J Hypertens 11: 80S-87S, 1998.
59.van Rijen HV, Eckardt D, Degen J, Theis M, Ott T, Willecke K, Jongsma HJ, Opthof T, and de Bakker JM:Slow conduction and enhanced anisotropy increase the propensity for ventricular tachyarrhythmias in adult mice with induced deletion of connexin43. Circulation 109: 1048-1055, 2004.
60.van Veen TA, Stein M, Royer A, Le Quang K, Charpentier F, Colledge WH, Huang CL, Wilders R, Grace AA, Escande D, de Bakker JM, and van Rijen HV: Impaired impulse propagation in Scn5a-
knockout mice: combined contribution of excitability, connexin expression, and tissue architecture in relation to aging. Circulation 112: 1927-1935, 2005.
61.Verdonck F, Volders PG, Vos MA, and Sipido KR:Increased Na+ concentration and altered Na/K pump activity in hypertrophied canine ventricular cells. Cardiovasc Res 57: 1035-1043, 2003.
62.Verkerk AO, Veldkamp MW, Bouman LN, and van Ginneken AC: Calcium-activated Cl- current contributes to delayed afterdepolarizations in single Purkinje and ventricular myocytes. Circulation 101: 2639-2644, 2000.
63.Volders PG, Kulcsar A, Vos MA, Sipido KR, Wellens HJ, Lazzara R, and Szabo B:Similarities between early and delayed afterdepolarizations induced by isoproterenol in canine ventricular myocytes. Cardiovasc Res 34: 348-359, 1997.
64.Waldo AL and Wit AL:Mechanisms of cardiac arrhythmias. Lancet 341: 1189-1193, 1993.
65.Wang DZ, Reiter RS, Lin JL, Wang Q, Williams HS, Krob SL, Schultheiss TM, Evans S, and Lin JJ:Requirement of a novel gene, Xin, in cardiac morphogenesis. Development 126: 1281-1294, 1999.
66.Wang X and Gerdes AM:Chronic pressure overload cardiac hypertrophy and failure in guinea pigs: III. Intercalated disc remodeling. J Mol Cell Cardiol 31: 333-343, 1999.
67.Wang Z, Nolan B, Kutschke W, and Hill JA:Na+-Ca2+ exchanger remodeling in pressure overload cardiac hypertrophy. J Biol Chem 276: 17706-17711, 2001.
68.Wu SH, Chen YC, Higa S and Lin CI:Oscillatory transient inward currents in ventricular myocytes of healthy versus myopathic Syrian hamster. Clin Exp Pharmacol Physiol 31: 668-676, 2004.
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1. <求學也是一種人格的考驗──宋濂的「送東陽馬生序」>,戴朝福,《中國語文》,459期,頁63-66,1985年9月。
2. <「元史」纂修若干問題辨析>,黃兆強 著,《東吳歷史學報》,第1期,頁153-179,1985年5月。
3. <宋濂「送東陽馬生序」探析>,余崇生 著,《中華文化復興月刊》,16卷9期,
4. <宋濂的經師氣象與人師風範>,戚宜君 著,《中華文藝》,第147期,頁55-61,1983年5月。
5. <宋濂詩論述評>,龔顯宗 著,《華學月刊》,第128期,頁31-35,1982年8月。
6. <宋濂──秦士錄>,江舉謙 著,《明道文藝》,第190期,頁60-67,1982年1月。
7. <學仕官名類釋(宋濂、方孝儒、王守仁、歸有光、楊繼盛、袁宏道、史可法)> ,李慕如 著,《今日中國》,第119期,頁131-144,1981年3月。
8. <明初大手筆宋濂>,杜若 著,《臺肥月刊》,第31卷第11期,頁40-42,1980年10月。 
9. <台﹖臺﹖治書御史﹖──談宋濂「秦士錄」注釋的小問題>,左德成 著,《國文天地》,第11卷第12期,頁111-112,1986年5月。
10. <宋濂的政治思想>,劉汝錫 著,《思與言》,第17卷第2期,頁63-71,1979年7月。
11. <劉基對宋濂的友誼及其「二鬼」詩索隱>,徐朔方 著,《中國書目季刊》,第13卷第3期1986年12月。
12. <劉基、宋濂遺事補正>,高越天 著,《浙江月刊》,第10卷第10期,頁35-36,1978年10月。
13. <記明初大儒宋濂>,王杰謀 著,《浙江月刊》,第3卷第1期,頁16,1971年1月。
14. <宋濂與徐達之死──明史中的兩樁懸案>,徐道鄰 著,《東方雜誌》,第1卷
15. <宋濂與道教>,龔顯宗 著,《道教學探索》,第6卷,頁396-407,1992年12。月。
 
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