Objective To characterize early afterdepolarizations （EADs） caused triggered activity （TA） among calsequestrin-2 （CASQ2） knock-in （CASQ2 KI） mice and its relationship with aging. Methods Electrophysiological p...Objective To characterize early afterdepolarizations （EADs） caused triggered activity （TA） among calsequestrin-2 （CASQ2） knock-in （CASQ2 KI） mice and its relationship with aging. Methods Electrophysiological properties of ventricular myocytes from 3- month （mo, young）, 9-mo （adult-l） and 12-too （adult-2） in wild-type （WT） and CASQ2 KI mice were investigated with patch-clamp technique. Results The incidences of EADs and TA in CASQ2 KI cardiomyocytes increased with increasing age. In contrast, WT mice cardiomyocytes showed no significant change in matched-age groups. Compared with that in 3-mo CASQ2 KI mice, the 50% repolarization of action potential （APD50） showed prolongation in both 9-mo and 12-mo ones （9.2±0.9 ms of 9-mo and 10.3 ± 1.2 ms of 12- mo vs. 5.6± 0.3 ms of 3-mo）, while the 90 % repolarization of action potential （APD90） was similar among 3 age groups. Compared with 3-mo mice, the 9-mo and 12-mo CASQ2 KI mice showed markedly reduced transient outward potassium current （Ito） densities but increased L-type calcium current （ICa-L） densities. Conlcusion This study suggested that events of EADs and TA in CASQ2 KI mice increased with increasing age, It might be associated partly with the augment of cellular calcium concentration and the prolongation of APD50 induced by decrease of Ito and increase of ICa-L in adult CASQ2 KI mice展开更多
AIM: To compare expression of Ca2+-regulating proteins in upper gastrointestinal (GI) tract of achalasia patients and healthy volunteers and to elucidate their role in achalasia. METHODS: Sarcoplasmic reticulum Ca2+ A...AIM: To compare expression of Ca2+-regulating proteins in upper gastrointestinal (GI) tract of achalasia patients and healthy volunteers and to elucidate their role in achalasia. METHODS: Sarcoplasmic reticulum Ca2+ ATPase (SERCA) isoforms 2a and 2b, phospholamban (PLB), calsequestrin (CSQ), and calreticulin (CRT) were assessed by quantitative Western blotting in esophagus and heart of rats, rabbits, and humans. Furthermore, expression profi les of these proteins in biopsies of lower esophageal sphincter and esophagus from patients with achalasia and healthy volunteers were analyzed. RESULTS: SERCA 2a protein expression was much higher in human heart (cardiac ventricle) compared to esophagus. However, SERCA 2b was expressed predominantly in the esophagus. The highest CRT expression was noted in the human esophagus, while PLB, although highly expressed in the heart, was below our detection limit in upper GI tissue. Compared to healthy controls, CSQ and CRT expression in lower esophageal sphincter and distal esophageal body were signif icantly reduced in patients with achalasia (P < 0.05). CONCLUSION: PLB in the human esophagus mightbe of lesser importance for regulation of SERCA than in heart. Lower expression of Ca2+ storage proteins (CSQ and CRT) might contribute to increased lower esophageal sphincter pressure in achalasia, possibly by increasing free intracellular Ca2+.展开更多
TNNI3K is a cardiac-specific and cardiac troponin I(cT n I)-interacting MAP kinase, known to play important roles in promoting cardiac differentiation, maintenance of beating rhythm and contractual force. The molecula...TNNI3K is a cardiac-specific and cardiac troponin I(cT n I)-interacting MAP kinase, known to play important roles in promoting cardiac differentiation, maintenance of beating rhythm and contractual force. The molecular structure of TNNI3 K contains three kinds of domain: a seven or ten NH2-terminal ankyrin repeat domain followed by a protein kinase domain and a COOH-terminal serine-rich domain. There are many binding sites in the structure of TNNI3 K for binding to ATP, magnesium, nucleotide, protein kinase C, antioxidant protein 1(AOP-1) and cT n I, indicating TNNI3 K has many interacting partners. This review summarizes the evidence, hypothesis and significance of TNNI3 K interacting with TNNI3 and its other putative interaction partners. From the literature, the interaction partners of TNNI3 K are divided into 2 types following their phenotypic pattern of functions, positive interaction(to increase the cardiac performance) or negative interaction(to suppress the cardiac performance). Following their binding sites, it also can be divided into other 2 types: binding to C-terminal domain(e.g., cT n I) or binding to both ankyrin repeat domain and C-terminal domains(AOP-1).To date, a well understood partner of TNNI3 K is cT nI, from the molecular structure, physiological function, mechanisms and its significance in some physiological and pathophysiological conditions. There are many reasons to believe that, with more understanding on the TNNI3 K interacting with its partners, we can understand more roles of TNNI3 K in some cardiac diseases.展开更多
文摘Objective To characterize early afterdepolarizations （EADs） caused triggered activity （TA） among calsequestrin-2 （CASQ2） knock-in （CASQ2 KI） mice and its relationship with aging. Methods Electrophysiological properties of ventricular myocytes from 3- month （mo, young）, 9-mo （adult-l） and 12-too （adult-2） in wild-type （WT） and CASQ2 KI mice were investigated with patch-clamp technique. Results The incidences of EADs and TA in CASQ2 KI cardiomyocytes increased with increasing age. In contrast, WT mice cardiomyocytes showed no significant change in matched-age groups. Compared with that in 3-mo CASQ2 KI mice, the 50% repolarization of action potential （APD50） showed prolongation in both 9-mo and 12-mo ones （9.2±0.9 ms of 9-mo and 10.3 ± 1.2 ms of 12- mo vs. 5.6± 0.3 ms of 3-mo）, while the 90 % repolarization of action potential （APD90） was similar among 3 age groups. Compared with 3-mo mice, the 9-mo and 12-mo CASQ2 KI mice showed markedly reduced transient outward potassium current （Ito） densities but increased L-type calcium current （ICa-L） densities. Conlcusion This study suggested that events of EADs and TA in CASQ2 KI mice increased with increasing age, It might be associated partly with the augment of cellular calcium concentration and the prolongation of APD50 induced by decrease of Ito and increase of ICa-L in adult CASQ2 KI mice
基金Supported by grants from the "Deutsche Forschungsgemeinschaft" (DFG) and the Interdisciplinary Center of Clinical Research (IZKF) Mnster
文摘AIM: To compare expression of Ca2+-regulating proteins in upper gastrointestinal (GI) tract of achalasia patients and healthy volunteers and to elucidate their role in achalasia. METHODS: Sarcoplasmic reticulum Ca2+ ATPase (SERCA) isoforms 2a and 2b, phospholamban (PLB), calsequestrin (CSQ), and calreticulin (CRT) were assessed by quantitative Western blotting in esophagus and heart of rats, rabbits, and humans. Furthermore, expression profi les of these proteins in biopsies of lower esophageal sphincter and esophagus from patients with achalasia and healthy volunteers were analyzed. RESULTS: SERCA 2a protein expression was much higher in human heart (cardiac ventricle) compared to esophagus. However, SERCA 2b was expressed predominantly in the esophagus. The highest CRT expression was noted in the human esophagus, while PLB, although highly expressed in the heart, was below our detection limit in upper GI tissue. Compared to healthy controls, CSQ and CRT expression in lower esophageal sphincter and distal esophageal body were signif icantly reduced in patients with achalasia (P < 0.05). CONCLUSION: PLB in the human esophagus mightbe of lesser importance for regulation of SERCA than in heart. Lower expression of Ca2+ storage proteins (CSQ and CRT) might contribute to increased lower esophageal sphincter pressure in achalasia, possibly by increasing free intracellular Ca2+.
文摘TNNI3K is a cardiac-specific and cardiac troponin I(cT n I)-interacting MAP kinase, known to play important roles in promoting cardiac differentiation, maintenance of beating rhythm and contractual force. The molecular structure of TNNI3 K contains three kinds of domain: a seven or ten NH2-terminal ankyrin repeat domain followed by a protein kinase domain and a COOH-terminal serine-rich domain. There are many binding sites in the structure of TNNI3 K for binding to ATP, magnesium, nucleotide, protein kinase C, antioxidant protein 1(AOP-1) and cT n I, indicating TNNI3 K has many interacting partners. This review summarizes the evidence, hypothesis and significance of TNNI3 K interacting with TNNI3 and its other putative interaction partners. From the literature, the interaction partners of TNNI3 K are divided into 2 types following their phenotypic pattern of functions, positive interaction(to increase the cardiac performance) or negative interaction(to suppress the cardiac performance). Following their binding sites, it also can be divided into other 2 types: binding to C-terminal domain(e.g., cT n I) or binding to both ankyrin repeat domain and C-terminal domains(AOP-1).To date, a well understood partner of TNNI3 K is cT nI, from the molecular structure, physiological function, mechanisms and its significance in some physiological and pathophysiological conditions. There are many reasons to believe that, with more understanding on the TNNI3 K interacting with its partners, we can understand more roles of TNNI3 K in some cardiac diseases.
