• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 1999년도 학술발표회 진행표 및 논문초록
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• pp.29-29
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• 1999

Diabetic cardiomyopathy has been suggested to be caused by the intracellular Ca$\^$2＋/ overload in the myocardium. We have investigated the possible mechanism of the functional defect of cardiac sarcoplasmic reticulum (SR) in diabetic rats with respect to Ca$\^$2＋/-ATPase and phospholamban (PLB) at the transcriptional and translational levels.(omitted)

• BMB Reports
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• 제46권5호
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• pp.237-243
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• 2013

Heart failure is one of the leading causes of sudden death in developed countries. While current therapies are mostly aimed at mitigating associated symptoms, novel therapies targeting the subcellular mechanisms underlying heart failure are emerging. Failing hearts are characterized by reduced contractile properties caused by impaired $Ca^{2+}$ cycling between the sarcoplasm and sarcoplasmic reticulum (SR). Sarcoplasmic/endoplasmic reticulum $Ca^{2+}$ ATPase 2a (SERCA2a) mediates $Ca^{2+}$ reuptake into the SR in cardiomyocytes. Of note, the expression level and/or activity of SERCA2a, translating to the quantity of SR $Ca^{2+}$ uptake, are significantly reduced in failing hearts. Normalization of the SERCA2a expression level by gene delivery has been shown to restore hampered cardiac functions and ameliorate associated symptoms in pre-clinical as well as clinical studies. SERCA2a activity can be regulated at multiple levels of a signaling cascade comprised of phospholamban, protein phosphatase 1, inhibitor-1, and $PKC{\alpha}$. SERCA2 activity is also regulated by post-translational modifications including SUMOylation and acetylation. In this review, we will highlight the molecular mechanisms underlying the regulation of SERCA2a activity and the potential therapeutic modalities for the treatment of heart failure.

• BMB Reports
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• 제51권8호
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• pp.378-387
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• 2018

Skeletal muscle contracts or relaxes to maintain the body position and locomotion. For the contraction and relaxation of skeletal muscle, $Ca^{2+}$ in the cytosol of skeletal muscle fibers acts as a switch to turn on and off a series of contractile proteins. The cytosolic $Ca^{2+}$ level in skeletal muscle fibers is governed mainly by movements of $Ca^{2+}$ between the cytosol and the sarcoplasmic reticulum (SR). Store-operated $Ca^{2+}$ entry (SOCE), a $Ca^{2+}$ entryway from the extracellular space to the cytosol, has gained a significant amount of attention from muscle physiologists. Orai1 and stromal interaction molecule 1 (STIM1) are the main protein identities of SOCE. This mini-review focuses on the roles of STIM proteins and SOCE in the physiological and pathophysiological functions of skeletal muscle and in their correlations with recently identified proteins, as well as historical proteins that are known to mediate skeletal muscle function.

• The Korean Journal of Physiology and Pharmacology
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• 제4권5호
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• pp.417-425
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• 2000

The underlying mechanism commonly applicable for both the positive and negative force-frequency relationships (FFR) was pursued in left atria (LA) of rat and rabbit. The species differences in the roles of $Na^+/Ca^{2+}$ exchanger and sarcoplasmic reticulum (SR), which are major intracellular $Ca^{2+}$ regulatory mechanisms in the heart, were examined in the amplitude accommodation to the frequency that changed from 3 Hz to the variable test frequencies for 5 minutes in the electrically field stimulated left atria (LA) of rat and rabbit. Norepinephrine strongly increased the frequency-related amplitude accommodation in both of rat and rabbit LA, while monensin, oubain or the reduced $Na^+$ and 0 mM $Ca^{2+}$ containing Tyrode solution increased the frequency-related amplitude accommodation only in the rabbit LA. Monenisn was also able to increase the frequency-related amplitude accommodation only in 1-day old rat LA but not in 4-week old rat LA that had 75% less $Na^+/Ca^{2+}$ exchanger with 97% higher SR than 1-day old rat LA. Taken together, it is concluded that the differences in the prevalence between myocardial $Na^+/Ca^{2+}$ exchanger and SR in the amplitude accommodation to the frequency-change determine the difference in the FFR between rat and rabbit heart.

• The Korean Journal of Physiology
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• 제21권2호
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• pp.179-189
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• 1987

Since it has been known that ryanodine has a potent negative inotropic effect on the cardiac muscle contractility (Jenden and Fairhurst, 1968), ryanodine has been a subject of intensive research (Frank and Sleator, 1975; Jones et al, 1978; Sutko et al, 1985). However, the underlying mechanism for the ryanodine dependent negative inotropic effect is still uncertain. In this study, the effects of ryanodine on the generation and relaxation of contracture due to Na-withdrawal and on the force-frequency relationship of heart muscles isolated from rats and guinea pigs were measured in an effort to understand the underlying mechanism of the ryanodine-induced negative inotropy. Results are summerized as follows: 1 ) Ryanodine significantly reduced the contractility of heart muscles produced at low frequency of stimulation, but showed a little effect on the contractility at high frequency stimulation. 2) Ryanodine, at the concentrations ranging from $10^{-6}\;M$ to $10^{-8}\;M$, had no significant effect on the Na-dependent relaxation of Na-withdrawl contracture. 3) Ryandoine significantly reduced the amplitude of the Na-withdrawl contracture, and this inhibitory effect was reinforced by procaine, antiagonized by caffeine and high potassium. From these results, it may be concluded that the negative inotropic effect of ryanodine is mainly due to an inhibition of calcium release from sarcoplasmic reticulum.

• 한국동물학회지
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• 제14권2호
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• pp.43-56
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• 1971

筋小胞體의 Ca 吸收能과 ATPase 活性을 各種 濃度의 K, Mg, caffeine, procaine, 및 quinine 존재하에서 측정하였다. ATP不在下에서 Ca吸收能은 K 또는 Mg의 농도가 증가함에 따라 低下된다. 그러나 ATP 존재하에서의 Ca吸收能은 K의 농도에는 거의 영향을 받지 않고, Mg의 농도가 증가함에 따라 현저히 증가한다. Caffeine과 procaine은 ATP 존재하의 Ca吸收能을 阻害하지만 quinine은 阻害하지 않는다. ATPase 活性은 K의 농도에는 영향을 받지 않으나 Mg의 존재에 의하여 증가된다. Caffeine, procaine 및 quinine은 이 活性에 거의 영향을 미치지 않는다.

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 2003년도 정기총회 및 학술발표회
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• pp.19-19
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• 2003

We have developed a cardiac cell model (Kyoto Model) for the sinoatrial node and ventricle, which is composed of a common set of kinetic equations of membrane ionic currents, Ca$\^$2+/dynamics of sarcoplasmic reticulum and contractile protein. To expand this model by including metabolic pathways, the intracellular ATP metabolism, which is pivotal in cardiac excitation - contraction coupling, was incorporated. ATP consumption by the sarcolemmal Na$\^$+/ pump and the Ca pump in the sarcoplasmic reticulum were calculated with stoichiometry of 3Na:2K:1ATP and 2Ca:1ATP, respectively. ATP consumption by contraction was estimated according to experimental data. Dependence of contraction on ATP and inorganic phosphate was modeled, based on data of skinned cardiac fiber. in production by mitochondrial oxidative phosphorylation was modified from Korzeniewski '||'&'||' Zoladz (2001), and creatine kinase and adenylate kinase reactions were incorporated. ATP dependence of ATP-sensitive K channel and L type Ca channel were also included.

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 2003년도 정기총회 및 학술발표회
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• pp.53-53
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• 2003

Calumenin was previously identified as a high affinity Ca$\^$2+/ binding protein in mouse cardiac sarcoplasmic reticulum (SR). For the present study, a 48 kDa skeletal homologue of calumenin was identified by sucrose-density gradient of rabbit skeletal SR membranes, concanavalin A treatment, 2D-gel electrophoresis, $\^$45/Ca$\^$2+/ overlay, Stains-all staining, and MALDI-TOF analysis. We attempted to clone the skeletal calumenin by RT-PCR based on mouse cardiac and human calumenin sequences. The deduced amino acid sequence (315 residues) of the skeletal calumenin showed high identity to mouse cardiac calumenin (90％). As seen in the cardiac calumenin, the deduced sequence contains a 19 amino acid N-terminal signal sequence and a HDEF C-terminal sequence, a putative retrieval signal to ER. Also, the skeletal calumenin contains one N-glycosylation site, three PKC phosphorylation sites, eight casein kinase 2 phosphorylation sites, and 6 EF-hand domains. GST-calumenin showed a conformational change and increased mobility in the presence of Ca$\^$2+/ in SDS-PAGE. Three calumenin interacting proteins (ryanodine receptor 1, glycogen phosphorylase, and phosphofructo kinase) were identified by pull-down assay with GST-calumenin and solubilized SR. All the interactions were Ca$\^$2+/dependent. The present results suggest that calumenin plays an important role in Ca$\^$2+/ homeostasis of muscle cells.

• Applied Microscopy
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• 제50권
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• pp.9.1-9.8
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• 2020

The fine structural characteristics of cardiac muscle cells and its myofibril organization in the orb web spider N. clavata were examined by transmission electron microscopy. Although myofibril striations are not remarkable as those of skeletal muscles, muscle fibers contain multiple myofibrils, abundant mitochondria, extensive sarcoplasmic reticulum and transverse tubules (T-tubules). Myofibrils are divided into distinct sarcomeres defined by Z-lines with average length of 2.0 ㎛, but the distinction between the A-band and the I-bands is not clear due to uniform striations over the length of the sarcomeres. Dyadic junction which consisted of a single T-tubule paired with a terminal cisterna of the sarcoplasmic reticulum is found mainly at the A-I level of sarcomere. Each cell is arranged to form multiple connections with neighboring cells through the intercalated discs. These specialized junctions include three types of intercellular junctions: gap junctions, fascia adherens and desmosomes for heart function. Our transmission electron microscopy (TEM) observations clearly show that spider's cardiac muscle contraction is controlled by neurogenic rather than myogenic mechanism since each cardiac muscle fiber is innervated by a branch of motor neuron through neuromuscular junctions.

• The Korean Journal of Physiology and Pharmacology
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• 제4권3호
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• pp.197-210
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• 2000

Suppressive role of $Na^+-Ca^{2+}$ exchange in myocardial tension generation was examined in the negative frequency-force relationship (FFR) of electric field stimulated left atria (LA) from postnatal developing rat heart and in the whole-cell clamped adult rat ventricular myocytes with high concentration of intracellular $Ca^{2+}$ buffer (14 mM EGTA). LA twitch amplitudes, which were suppressed by cyclopiazonic acid in a postnatal age-dependent manner, elicited frequency-dependent and postnatal age-dependent enhancements after $Na^+-reduced,\;Ca^{2+}-depleted$ (26 Na-0 Ca) buffer application. These enhancements were blocked by caffeine pretreatment with postnatal age-dependent intensities. In the isolated rat ventricular myocytes, stimulation with the voltage protocol roughly mimicked action potential generated a large inward current which was partially blocked by nifedipine or $Na^+$ current inhibition. 0 Ca application suppressed the inward current by $39{\pm}4%$ while the current was further suppressed after 0 Na-0 Ca application by $53{\pm}3%.$ Caffeine increased this inward current by $44{\pm}3%$ in spite of 14 mM EGTA. Finally, the $Na^+$ current-dependent fraction of the inward current was increased in a stimulation frequency-dependent manner. From these results, it is concluded that the $Ca^{2+}$ exit-mode (forward-mode) $Na^+-Ca^{2+}$ exchange suppresses the LA tension by extruding $Ca^{2+}$ out of the cell right after its release from sarcoplasmic reticulum (SR) in a frequency-dependent manner during contraction, resulting in the negative frequency-force relationship in the rat LA.