1.Inhibitory effect of Mg2+ on the release of Ca2+ from Ryanodine receptor of the sarcoplasmic reticulum in the skeletal muscle.
The Korean Journal of Thoracic and Cardiovascular Surgery 1992;25(4):347-355
No abstract available.
Muscle, Skeletal*
;
Ryanodine Receptor Calcium Release Channel*
;
Ryanodine*
;
Sarcoplasmic Reticulum*
3.Ca(2+)-induced Ca2+ Release from Internal Stores in INS-1 Rat Insulinoma Cells.
Kyung Jin CHOI ; Dong Su CHO ; Ju Young KIM ; Byung Joon KIM ; Kyung Moo LEE ; Shin Hye KIM ; Dong Kwan KIM ; Se Hoon KIM ; Hyung Seo PARK
The Korean Journal of Physiology and Pharmacology 2011;15(1):53-59
The secretion of insulin from pancreatic beta-cells is triggered by the influx of Ca2+ through voltage-dependent Ca2+ channels. The resulting elevation of intracellular calcium ([Ca2+]i) triggers additional Ca2+ release from internal stores. Less well understood are the mechanisms involved in Ca2+ mobilization from internal stores after activation of Ca2+ influx. The mobilization process is known as calcium-induced calcium release (CICR). In this study, our goal was to investigate the existence of and the role of caffeine-sensitive ryanodine receptors (RyRs) in a rat pancreatic beta-cell line, INS-1 cells. To measure cytosolic and stored Ca2+, respectively, cultured INS-1 cells were loaded with fura-2/AM or furaptra/AM. [Ca2+]i was repetitively increased by caffeine stimulation in normal Ca2+ buffer. However, peak [Ca2+]i was only observed after the first caffeine stimulation in Ca2+ free buffer and this increase was markedly blocked by ruthenium red, a RyR blocker. KCl-induced elevations in [Ca2+]i were reduced by pretreatment with ruthenium red, as well as by depletion of internal Ca2+ stores using cyclopiazonic acid (CPA) or caffeine. Caffeine-induced Ca2+ mobilization ceased after the internal stores were depleted by carbamylcholine (CCh) or CPA. In permeabilized INS-1 cells, Ca2+ release from internal stores was activated by caffeine, Ca2+, or ryanodine. Furthermore, ruthenium red completely blocked the CICR response in permeabilized cells. RyRs were widely distributed throughout the intracellular compartment of INS-1 cells. These results suggest that caffeine-sensitive RyRs exist and modulate the CICR response from internal stores in INS-1 pancreatic beta-cells.
Animals
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Caffeine
;
Calcium
;
Carbachol
;
Cytosol
;
Indoles
;
Insulin
;
Insulinoma
;
Rats
;
Ruthenium Red
;
Ryanodine
;
Ryanodine Receptor Calcium Release Channel
7.Clinical and genetic analysis of five children with Catecholaminergic polymorphic ventricular tachycardia due to variants of RYR2 gene.
Qiqing SUN ; Fangjie WANG ; Ruili ZHENG ; Zhenhua XIE ; Lijuan JIA ; Dongxiao LI
Chinese Journal of Medical Genetics 2023;40(8):960-965
OBJECTIVE:
To explore the clinical and genetic characteristics of five children with Catecholaminergic polymorphic ventricular tachycardia (CPVT).
METHODS:
Five children with clinical manifestations consistent with CPVT admitted to the Department of Cardiology of Children's Hospital Affiliated to Zhengzhou University from November 2019 to November 2021 were selected as the study subjects. Their clinical data were collected. Potential variants were detected by whole exome sequencing, and Sanger sequencing was used to verify the candidate variants. All patients were treated with β-blocker propranolol and followed up.
RESULTS:
All patients had developed the disease during exercise and presented with syncope as the initial clinical manifestation. Electrocardiogram showed sinus bradycardia. The first onset age of the 5 patients were (10.4 ± 2.19) years, and the time of delayed diagnosis was (1.6 ± 2.19) years. All of the children were found to harbor de novo heterozygous missense variants of the RYR2 gene, including c.6916G>A (p.V2306I), c.527G>C (p.R176P), c.12271G>A (p.A4091T), c.506G>T (p.R169L) and c.6817G>A (p.G2273R). Among these, c.527G>C (p.R176P) and c.6817G>A (p.G2273R) were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.527G>C (p.R176P) was classified as a pathogenic variant (PS2+PM1+PM2_Supporting+PM5+PP3+PP4), and the c.6817G>A (p.G2273R) was classified as a likely pathogenic variant (PS2+PM2_Supporting+PP3+PP4). The symptoms of all children were significantly improved with the propranolol treatment, and none has developed syncope during the follow up.
CONCLUSION
Discovery of the c.527G>C (p.R176P) and c.6817G>A (p.G2273R) variants has expanded the mutational spectrum of the RYR2 gene. Genetic testing of CPVT patients can clarify the cause of the disease and provide a reference for their genetic counseling.
Child
;
Humans
;
Mutation
;
Propranolol
;
Ryanodine Receptor Calcium Release Channel/genetics*
;
Syncope
;
Tachycardia, Ventricular/diagnosis*
;
United States
10.Na+-Ca2+ Exchange Curtails Ca2+ before Its Diffusion to Global Ca2+i in the Rat Ventricular Myocyte.
The Korean Journal of Physiology and Pharmacology 2005;9(2):95-101
In the heart, Na+-Ca2+ exchange (NCX) is the major Ca2+ extrusion mechanism. NCX has been considered as a relaxation mechanism, as it reduces global [Ca2+]i raised during activation. However, if NCX locates in the close proximity to the ryanodine receptor, then NCX would curtail Ca2+ before its diffusion to global Ca2+i. This will result in a global [Ca2+]i decrease especially during its ascending phase rather than descending phase. Therefore, NCX would decrease the myocardial contractility rather than inducing relaxation in the heart. This possibility was examined in this study by comparing NCX-induced extrusion of Ca2+ after its release from SR in the presence and absence of global Ca2+i transient in the isolated single rat ventricular myocytes by using patch-clamp technique in a whole-cell configuration. Global Ca2+i transient was controlled by an internal dialysis with different concentrations of BAPTA added in the pipette. During stimulation with a ramp pulse from +100 mV to -100 mV for 200 ms, global Ca2+i transient was suppressed only mildly, and completely at 1 mmol/L, and 10 mmol/L BAPTA, respectively. In these situations, ryanodine-sensitive inward NCX current was compared using 100micromol/L ryanodine, Na+ depletion, 5 mmol/L NiCl2 and 1micromol/L nifedipine. Surprisingly, the result showed that the ryanodine-sensitive inward NCX current was well preserved after 10 mmol/L BAPTA to 91 % of that obtained after 1 mmol/L BAPTA. From this result, it is concluded that most of the NCX-induced Ca2+ extrusion occurs before the Ca2+ diffuses to global Ca2+i in the rat ventricular myocyte.
Animals
;
Architectural Accessibility
;
Dialysis
;
Diffusion*
;
Heart
;
Muscle Cells*
;
Nifedipine
;
Patch-Clamp Techniques
;
Rats*
;
Relaxation
;
Ryanodine
;
Ryanodine Receptor Calcium Release Channel
Result Analysis
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