Oral administration of TRPV4 inhibitor improves atrial calcium handling abnormalities in sterile pericarditis rats / 生理学报

Atrial Ca2+ handling abnormalities, mainly involving the dysfunction of ryanodine receptor (RyR) and sarcoplasmic reticulum Ca2+-ATPase (SERCA), play a role in the pathogenesis of atrial fibrillation (AF). Previously, we found that the expression and function of transient receptor potential vanilloid subtype 4 (TRPV4) are upregulated in a sterile pericarditis (SP) rat model of AF, and oral administration of TRPV4 inhibitor GSK2193874 alleviates AF in this animal model. The aim of this study was to investigate whether oral administration of GSK2193874 could alleviate atrial Ca2+ handling abnormalities in SP rats. A SP rat model of AF was established by daubing sterile talcum powder on both atria of Sprague-Dawley (SD) rats after a pericardiotomy, to simulate the pathogenesis of postoperative atrial fibrillation (POAF). On the 3rd postoperative day, Ca2+ signals of atria were collected in isolated perfused hearts by optical mapping. Ca2+ transient duration (CaD), alternan, and the recovery properties of Ca2+ transient (CaT) were quantified and analyzed. GSK2193874 treatment reversed the abnormal prolongation of time to peak (determined mainly by RyR activity) and CaD (determined mainly by SERCA activity), as well as the regional heterogeneity of CaD in SP rats. Furthermore, GSK2193874 treatment relieved alternan in SP rats, and reduced its incidence of discordant alternan (DIS-ALT). More importantly, GSK2193874 treatment prevented the reduction of the S2/S1 CaT ratio (determined mainly by RyR refractoriness) in SP rats, and decreased its regional heterogeneity. Taken together, oral administration of TRPV4 inhibitor alleviates Ca2+ handling abnormalities in SP rats primarily by blocking the TRPV4-Ca2+-RyR pathway, and thus exerts therapeutic effect on POAF.

Desmin-related myopathy: report of a rare case.

The Protein Surplus Myopathies (PSM) are characterized by accumulation of protein aggregates, identifiable ultrastructurally, resulting due to mutations of the encoding genes. Desmin-related myopathies (DRM) are a form of PSM characterized by mutations of the desmin gene resulting in the formation of protein aggregates comprising mutant protein desmin and disturbance of the regular desmin intermediate network in the muscle fibers. We describe a rare case of DRM in a 23-year-old man who presented with complaints of difficulty in climbing stairs and running since the age of 5 years. EMG studies revealed a myopathic pattern. Muscle biopsy showed the features of muscular dystrophy with bluish rimmed vacuoles and sarcoplasmic inclusions, which were immunoreactive to desmin. Ultrastructural examination showed sarcoplasmic bodies and granulofilamentous inclusions. Although rare, the possibility of DRM/desminopathy should be considered in the presence of bluish rimmed vacuoles on light microscopy and characteristic ultrastructural inclusions. To the best of our knowledge this is the first case of DRM/desminopathy reported from India.

Ultrastructural variations in frog muscles subjected to sciatectomy.

Fine structural variations in two different types of muscles of frog (Rana cyanophlictis) subjected to sciatectomy were studied electronmicroscopically. Gastrocnemius muscle showed marked myofibrillar disarray and degeneration due to sciatectomy, while sartorius muscle was relatively less affected. The extent of sciatectomy induced fine structural variation was in proportion to the degree of denervation atrophy (as reflected by loss of wet muscle weight) in these muscles. Differences in the degree of degenerative changes in atrophying muscles may be attributed to variations in fiber type composition and stretch effects imposed during swimming movements.

Myoepithelial cells from a polychaete worm

Las células mioepiteliales que forman el proventriculo del polqueto Syllis spongiphila son interesantes morfológica y fisiológicamente. Cada célula consta de una región periférica, contractil y estriada, y una región central no contractil. La primera contiene uno o dos sarcómeros de una longitud de hasta 40 um. Cada filamento grueso (paramiosina) de unas 25 um de longitud, está rodeado de unos 20 miofilamentos finos. La región central encierra el núcleo, mitocondrias y vesículas llenas de un material cristalino. Experimentos con EGTA y "electron-probe analysis" demuestran que el Ca es el catión mas abundante en las vesículas, que son capaces de secuestrar calcio libre. Las células poseen un sistema tubular muy extenso, pero su retículo sarcoplásmico es rudimentario. Las células estas acopladas eléctricamente y reciben inervación excitadora (colinérgica) e inhibidora; se contraen al despolarizarse y se relajan al hiperpolarizarse, siendo capaces de producir potenciales de acción en los que la carga es llevada por iones de calcio. Sus canales par a calcio permiten el paso no solo de Ca, sino también de iones de Sr, Ba y Mn. en soluciones libres de calcio los potenciales de acción de Sr, Ba y Mn son de mayor duración que los Ca, pero solo los de Sr. producen contracción. experimentos con iones de Fe, Co y Ni suportan la idea de que la especifidad de los canales de Ca depende de su capacidad para distinguir las energias de hidratación de una población de cationes similares