scholarly journals Effect of dantrolene sodium on skeletal, cardiac, smooth muscles and their sarcoplasmic reticulum

1976 ◽  
Vol 26 ◽  
pp. 164
Author(s):  
Atsuko Suzuki ◽  
Ken Hotta
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Smooth Muscles ◽  
Dantrolene Sodium

Sarcoplasmic Reticulum Function in Smooth Muscle

2010 ◽  
Vol 90 (1) ◽  
pp. 113-178 ◽  
Author(s):  
Susan Wray ◽  
Theodor Burdyga
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Physiological Activity ◽  
Smooth Muscles ◽  
Outward Current ◽  
Integrated Approach ◽  
Transient Outward Current ◽  
Coupling Mechanism ◽  
Striated Muscles ◽  
Development And Aging

The sarcoplasmic reticulum (SR) of smooth muscles presents many intriguing facets and questions concerning its roles, especially as these change with development, disease, and modulation of physiological activity. The SR's function was originally perceived to be synthetic and then that of a Ca store for the contractile proteins, acting as a Ca amplification mechanism as it does in striated muscles. Gradually, as investigators have struggled to find a convincing role for Ca-induced Ca release in many smooth muscles, a role in controlling excitability has emerged. This is the Ca spark/spontaneous transient outward current coupling mechanism which reduces excitability and limits contraction. Release of SR Ca occurs in response to inositol 1,4,5-trisphosphate, Ca, and nicotinic acid adenine dinucleotide phosphate, and depletion of SR Ca can initiate Ca entry, the mechanism of which is being investigated but seems to involve Stim and Orai as found in nonexcitable cells. The contribution of the elemental Ca signals from the SR, sparks and puffs, to global Ca signals, i.e., Ca waves and oscillations, is becoming clearer but is far from established. The dynamics of SR Ca release and uptake mechanisms are reviewed along with the control of luminal Ca. We review the growing list of the SR's functions that still includes Ca storage, contraction, and relaxation but has been expanded to encompass Ca homeostasis, generating local and global Ca signals, and contributing to cellular microdomains and signaling in other organelles, including mitochondria, lysosomes, and the nucleus. For an integrated approach, a review of aspects of the SR in health and disease and during development and aging are also included. While the sheer versatility of smooth muscle makes it foolish to have a “one model fits all” approach to this subject, we have tried to synthesize conclusions wherever possible.

Sarcoplasmic reticulum and mitochondria as cation accumulation sites in smooth muscle

1973 ◽  
Vol 265 (867) ◽  
pp. 17-23 ◽  
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Divalent Cation ◽  
Electromechanical Coupling ◽  
Surface Membrane ◽  
Smooth Muscles ◽  
Relative Volume ◽  
Electron Dense Material ◽  
Tubular System ◽  
Central Elements

A tubular system of sarcoplasmic reticulum that is not penetrated by extracellular markers is described in vertebrate smooth muscles. The sarcoplasmic reticulum forms fenestrations around the surface vesicles and also forms close appositions (an approximately 10 to 12 nm gap traversed by periodic electron dense material) with the non-specialized surface membrane. The morphological couplings are considered to be the most probable sites of electromechanical coupling of the action potential to the twitch contraction. The relative volume of the sarcoplasmic reticulum varies in functionally different (tonic and phasic) smooth muscles, and correlates with the ability of the different smooth muscles to contract in the absence of extracellular calcium. Electron opaque deposits of strontium are accumulated by peripheral and central elements of the sarcoplasmic reticulum. The accumulation of strontium and barium by mitochondria raises the possibility that, in addition to the sarcoplasmic reticulum, mitochondria may play a role in the regulation of intracellular divalent cation levels in vertebrate smooth muscle.

739SERCA2 Cys674 modification lead to ventricular arrhythmia due to impaired sarcoplasmic reticulum Ca2+ handling

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
K Ito ◽  
H Yada ◽  
T Toya ◽  
A Osaki ◽  
K Kagami ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Ventricular Arrhythmia ◽  
Pathological Condition ◽  
Electrophysiological Study ◽  
Intraperitoneal Administration ◽  
Oxidative Modification ◽  
Qtc Interval ◽  
Dantrolene Sodium ◽  
High Incidence ◽  
Transient Measurement

Abstract Background Sarcoplasmic reticulum Ca2+-ATPase2 (SERCA2) plays an important role in intracellular Ca2+ handling. Under pathological conditions, oxidative stress leads to irreversible oxidation of Cys674 on SERCA2 which causes intracellular Ca2+ overload. Intracellular Ca2+ overload is known as the cause of ventricular arrhythmia, but the relation between SERCA2 function and ventricular arrhythmia remains unclear. Purpose To investigate the role of Cys674 on SERCA2 in the intracellular Ca2+ handling and the induction of ventricular arrhythmia. Methods We employed SERCA2 Cys674Ser heterozygote knock-in mice (SKI) which mimics oxidative modification of Cys674 on SERCA2. Continuous infusion of angiotensin (ANG) (3mg/kg/day) or distilled water were performed both in wild type mice (WT) and SKI for a week. After 1 week, electrophysiological study and intracellular Ca2+ transient measurement were performed. Results ANG elevated blood pressure and represented cardiac hypertrophy with fibrosis similarly both in WT and SKI. The mRNA expression of calcium/calmodulin-dependent protein kinase-II (CaMKII), ryanodine receptor (RyR) and sodium-calcium exchanger (NCX) was increased in SKI heart compared with WT. QTc interval was prolonged in SKI compared with WT, which was markedly prolonged with ANG infusion. Under programmed electrical stimulation, only SKI with ANG showed high incidence of pacing induced ventricular arrhythmia (0/11 in WT/SKI control, 0/14 in WT with ANG vs. 8/14 in SKI with ANG, P < 0.01). In Ca2+ transient measurement, the peak Ca2+ transient amplitude (F/F0) was decreased (WT: 1.81 vs. SKI: 1.46, P < 0.01) and the time to 50% of cytosolic Ca2+ extrusion (T50) was prolonged (WT: 152.6ms vs. SKI: 202.3ms, P < 0.05) in SKI with ANG, suggesting decreased sarcoplasmic reticulum Ca2+ content and impaired SERCA2 activity in SKI with ANG. Intraperitoneal administration of dantrolene sodium (DAN) which inhibit Ca2+ leakage from RyR receptor normalized decreased F/F0 and prolonged T50 in SKI with ANG (Fig. 1 A, B). DAN also prevented QTc prolongation and decreased the incidence of ventricular arrhythmia in SKI with ANG (8/14 in SKI with ANG vs. 2/13 in SKI with ANG + DAN, P < 0.05) (Fig. 2). Conclusions The loss of thiol on Cys674 under pathological condition resulted in impaired Ca2+ handling and high incidence of ventricular arrhythmia which were ameliorated by inhibition of Ca2+ leakage through RyR. Oxidative modification of Cys674 on SERCA2 might contribute to Ca2+ mishandling and arrhythmogenesis. Abstract Figure.

scholarly journals SARCOPLASMIC RETICULUM AND EXCITATION-CONTRACTION COUPLING IN MAMMALIAN SMOOTH MUSCLES

1972 ◽  
Vol 52 (3) ◽  
pp. 690-718 ◽  
Author(s):  
Carrick E. Devine ◽  
Avril V. Somlyo ◽  
Andrew P. Somlyo
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Pulmonary Artery ◽  
Mesenteric Artery ◽  
Electromechanical Coupling ◽  
Surface Membrane ◽  
Main Pulmonary Artery ◽  
Smooth Muscles ◽  
Taenia Coli ◽  
Virtual Absence ◽  
Mesenteric Vein

The sarcoplasmic reticulum (SR) was studied in the smooth muscles of rabbit main pulmonary artery, mesenteric vein, aorta, mesenteric artery, taenia coli, guinea pig mesenteric artery, and human uterus, and correlated with contractions of the smooth muscles in Ca-free media. SR volumes were determined in main pulmonary artery (5.1%), aorta (5%), portal-anterior mesenteric vein (2.2%), taenia coli (2%), and mesenteric artery (1.8%): because of tangentially sectioned membranes these estimates are subject to a correction factor of up to +50% of the values measured. Smooth muscles that contained a relatively large volume of SR maintained significant contractile responses to drugs in the virtual absence of extracellular calcium at room temperatures, while smooth muscles that had less SR did not. The unequal maximal contractions of main pulmonary artery elicited by different drugs were also observed in Ca-free, high potassium-depolarizing solution, indicating that they were secondary to some mechanism independent of changes in membrane potential or calcium influx. Longitudinal tubules of SR run between and are fenestrated about groups of surface vesicles separated from each other by intervening dense bodies. Extracellular markers (ferritin and lanthanum) entered the surface vesicles, but not the SR. The peripheral SR formed couplings with the surface membrane: the two membranes were separated by gaps of approximately 10 nm traversed by electron-opaque connections suggestive of a periodicity of approximately 20–25 nm. These couplings are considered to be the probable sites of electromechanical coupling in twitch smooth muscles. Close contacts between the SR and the surface vesicles may have a similar function, or represent sites of calcium extrusion. The presence of both thick and thin myofilaments and of rough SR in smooth muscles supports the dual, contractile and morphogenetic, function of smooth muscle.

The sphincter pupillae of the guinea-pig: structure of muscle cells, intercellular relations and density of innervation

1974 ◽  
Vol 186 (1085) ◽  
pp. 369-386 ◽  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cell Surface ◽  
Guinea Pig ◽  
Cell Volume ◽  
Muscle Cell ◽  
Smooth Muscles ◽  
Volume Ratio ◽  
Muscle Cells ◽  
Structural Features ◽  
Full Cross Section

Compared with those of visceral and vascular smooth muscles, the smooth muscle cells of the sphincter pupillae of the guinea-pig show remarkable structural features. They are small, irregular in shape, and have a surface to volume ratio of about 2.73 (i. e. for every cubic micrometre of cell volume there are on average 2.73 µ m 2 of cell surface). Mitochon­dria constitute about 12% of the cell volume. Smooth sarcoplasmic reticulum is extremely well developed, lying underneath wide areas of the cell surface, between and around caveolae, and around most mitochondria. Stacks of cisternae of sarcoplasmic reticulum are present in superficial and deep regions of muscle cells. In some muscle cells rough sarcoplasmic reticulum is predominant. Thick, thin and intermediate myofilaments are readily seen in all preparations. A few cells showed myofilaments with size and arrangement similar to those of striated muscle. Nexuses are frequently associated with sacs of sarcoplasmic reticulum and are more numerous than in smooth muscles previously studied. In montages of cross-sectioned sphincters about 24 nexuses for 100 muscle cells are counted. Frequently two parts of the same cell are connected by a nexus. Nexuses also occur between muscle cells which are in close relationship with the same nerve varicosity. The density of innervation is very high. In a montage from a full cross-section of the sphincter, there are 2791 profiles of muscle cells and 843 nerve fibres, of which 425 contain synaptic vesicles and 194 are separated from muscle cells by a gap of only about 20 nm. In a number of the closely apposed nerve endings junctional specializations are seen. Collagen fibrils have a diameter of about 50 nm. Some bundles of collagen lie between the muscle cell membrane and the basal lamina. Melanocytes and a few fibroblasts are seen. Blood vessels do not penetrate into the muscle but are numerous around it. No muscle cell is more than 20 µ m away from the nearest capillary. Endothelial cells contain abundant microfilaments 10 nm in diameter. Capillaries are not fenestrated.

CaM kinase II and phospholamban contribute to caffeine-induced relaxation of murine gastric fundus smooth muscle

2005 ◽  
Vol 288 (6) ◽  
pp. C1202-C1210 ◽  
Author(s):  
Minkyung Kim ◽  
Sang Yun Cho ◽  
In Soo Han ◽  
Sang Don Koh ◽  
Brian A. Perrino
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Channel Blocker ◽  
Muscle Tone ◽  
Smooth Muscles ◽  
Cyclopiazonic Acid ◽  
Gastric Fundus ◽  
Cam Kinase Ii ◽  
Cam Kinase ◽  
Camkii Activation

Caffeine has been shown to increase the Ca2+ release frequency (Ca2+ sparks) from the sarcoplasmic reticulum (SR) through ryanodine-sensitive stores and relax gastric fundus smooth muscle. Increased Ca2+ store refilling increases the frequency of Ca2+ release events and store refilling is enhanced by CaM kinase II (CaMKII) phosphorylation of phospholamban (PLB). These findings suggest that transient, localized Ca2+ release events from the SR may activate CaMKII and contribute to relaxation by enhancing store refilling due to PLB Thr17 phosphorylation. To investigate this possibility, we examined the effects of caffeine on CaMKII, muscle tone, and PLB phosphorylation in murine gastric fundus smooth muscle. Caffeine (1 mM) hyperpolarized and relaxed murine gastric fundus smooth muscle and activated CaMKII. Ryanodine, tetracaine, or cyclopiazonic acid each prevented CaMKII activation and significantly inhibited caffeine-induced relaxation. The large-conductance Ca2+-activated K+ channel blocker iberiotoxin, but not apamin, partially inhibited caffeine-induced relaxation. Caffeine-induced CaMKII activation increased PLB Thr17, but not PLB Ser16 phosphorylation. 3-Isobutyl-1-methylxanthine increased PLB Ser16 phosphorylation, but not PLB Thr17 phosphorylation. The CaMKII inhibitor KN-93 inhibited caffeine-induced relaxation and PLB Thr17 phosphorylation. These results show that caffeine-induced CaMKII activation and PLB phosphorylation play a role in the relaxation of gastric fundus smooth muscles.

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