Tomo Matsumoto

Comparison of expression of connexin in right atrial myocardium in patients with chronic atrial fibrillation versus those in sinus rhythm

An abnormal distribution of the gap junction occurs in chronic atrial fibrillation (AF). There are conflicting data regarding changes in connexins (Cxs) in experimental models of AF. We examined whether patients with chronic AF have alterations in atrial Cxs. We analyzed the expression of Cx40 and Cx43 in the right atrial myocardium from 10 patients with mitral valvular disease (MVD) who had AF (MVD/AF), 10 patients with MVD who were in normal sinus rhythm (MVD/NSR), and 10 control patients in NSR (tissue obtained during coronary artery bypass surgery). Hemodynamic and echocardiographic data were obtained before surgery, and an electrophysiologic examination was performed during the operation. An immunohistochemical study was performed on atrial tissue. The relative expression level of Cx40 protein was significantly lower in MVD/AF patients (6.5 +/- 4.6) than in either MVD/NSR patients (17.7 +/- 8.9, p <0.05) or controls (24.7 +/- 11.1, p <0.01). The relative expression level of Cx40 messenger ribonucleic acid was also significantly lower in MVD/AF patients (0.23 +/- 0.13) than in MVD/NSR patients (0.47 +/- 0.26, p <0.01) or controls (0.47 +/- 0.17, p <0.01). For Cx43 protein and messenger ribonucleic acid, there was no significant difference in relative expression levels among the 3 groups. Interestingly, the level of serine-phosphorylated Cx40 was approximately 52% greater in MVD/AF patients than in controls. In MVD/AF patients, the immunoreactive signal of Cx40 was significantly lower than in controls. There was no significant difference in the connective tissue-volume fraction among the groups. Thus, downregulation of Cx40 and abnormal phosphorylation of Cx40 may result in abnormal cell-to-cell communication and alteration in the electrophysiologic properties of the atrium, leading to the initiation and/or perpetuation of AF.

Sorcin interacts with sarcoplasmic reticulum Ca2+–ATPase and modulates excitation–contraction coupling in the heart

Abstract Sorcin is a 21.6–kDa Ca2+ binding protein of the penta–EF hand family. Several studies have shown that sorcin modulates multiple proteins involved in excitation–contraction (E–C) coupling in the heart, such as the cardiac ryanodine receptor (RyR2), L–type Ca2+ channel, and Na+–Ca2+ exchanger, while it has also been shown to be phosphorylated by cAMP–dependent protein kinase (PKA). To elucidate the effects of sorcin and its PKA–dependent regulation on E–C coupling in the heart, we identified the PKA–phosphorylation site of sorcin, and found that serine178 was preferentially phosphorylated by PKA and dephosphorylated by protein phosphatase– 1. Isoproterenol allowed sorcin to translocate to the sarcoplasmic reticulum (SR). In addition, adenovirus–mediated overexpression of sorcin in adult rat cardiomyocytes significantly increased both the rate of decay of the Ca2+ transient and the SR Ca2+ load. An assay of oxalate–facilitated Ca2+ uptake showed that recombinant sorcin increased Ca2+ uptake in a dose–dependent manner. These data suggest that sorcin activates the Ca2+–uptake function in the SR. In UM–X7. 1 cardiomyopathic hamster hearts, the relative amount of sorcin was significantly increased in the SR fraction, whereas it was significantly decreased in whole–heart homogenates. In failing hearts, PKA–phosphorylated sorcin was markedly increased, as assessed using a back–phosphorylation assay with immunoprecipitated sorcin. Our results suggest that sorcin activates Ca2+–ATPase–mediated Ca2+ uptake and restores SR Ca2+ content, and may play critical roles in compensatory mechanisms in both Ca2+ homeostasis and cardiac dysfunction in failing hearts.

Relation Between Microvolt-Level T-Wave Alternans and Cardiac Sympathetic Nervous System Abnormality Using Iodine-123 Metaiodobenzylguanidine Imaging in Patients With Idiopathic Dilated Cardiomyopathy

We examined the relation between microvolt-level T-wave alternans and cardiac sympathetic nervous system abnormality using iodine-123 metaiodobenzylguanidine imaging in patients with idiopathic dilated cardiomyopathy. Our results strongly indicate that cardiac sympathetic denervation and accelerated sympathetic nervous activity play important roles in the presence of microvolt-level T-wave alternans in patients with idiopathic-dilated cardiomyopathy.