Effects of hyperthyroidism on delayed rectifier K+ currents in left and right murine atria

2005 ◽  
Vol 289 (4) ◽  
pp. H1448-H1455 ◽  
Author(s):  
Ying Hu ◽  
S. V. Penelope Jones ◽  
Wolfgang H. Dillmann

Hyperthyroidism has been associated with atrial fibrillation (AF); however, hyperthyroidism-induced ion channel changes that may predispose to AF have not been fully elucidated. To understand the electrophysiological changes that occur in left and right atria with hyperthyroidism, the patch-clamp technique was used to compare action potential duration (APD) and whole cell currents in myocytes from left and right atria from both control and hyperthyroid mice. Additionally, RNase protection assays and immunoblotting were performed to evaluate the mRNA and protein expression levels of K+ channel α-subunits in left and right atria. The results showed that 1) in control mice, the APD was shorter and the ultra-rapid delayed rectifier K+ conductance ( IKur) and the sustained delayed rectifier K+ conductance ( Iss) were larger in the left than in the right atrium; also, mRNA and protein expression levels of Kv1.5 and Kv2.1 were higher in the left atrium; 2) in hyperthyroid mice, the APD was shortened and IKur and Iss were increased in both left and right atrial myocytes, and the protein expression levels of Kv1.5 and Kv2.1 were increased significantly in both atria; and 3) the influence of hyperthyroidism on APD and delayed rectifier K+ currents was more prominent in right than in left atrium, which minimized the interatrial APD difference. In conclusion, hyperthyroidism resulted in more significant APD shortening and greater delayed rectifier K+ current increases in the right vs. the left atrium, which can contribute to the propensity for atrial arrhythmia in hyperthyroid heart.

1956 ◽  
Vol 186 (3) ◽  
pp. 521-524 ◽  
Author(s):  
A. van Harreveld ◽  
F. E. Russell

The mean left and right atrial pressures were measured in six groups of 10 kittens each. One group was examined between the 12th and 24th hour after birth, one group after 3 days, after 1 week, 2 weeks, 1 month and 2 months. The left and right atrial pressures were almost equal in the first group. With age an increasing left to right pressure gradient developed. In the oldest group the pressure in the left atrium was almost twice as great as in the right. Parallel with the pressure gradient a difference developed in the wall thicknesses of the left and right ventricles. At birth the ventricular walls were of about equal thickness; at age 2 months the left ventricle wall was more than twice as thick as the right. The relationship between ventricle wall thicknesses and atrial pressures is discussed.


PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248951
Author(s):  
Gurpreet Singh Dhillon ◽  
Nikhil Ahluwalia ◽  
Shohreh Honarbakhsh ◽  
Adam Graham ◽  
Antonio Creta ◽  
...  

Background We evaluated the effect of adenosine upon mechanisms sustaining persistent AF through analysis of contact electrograms and ECGI mapping. Methods Persistent AF patients undergoing catheter ablation were included. ECGI maps and cycle length (CL) measurements were recorded in the left and right atrial appendages and repeated following boluses of 18 mg of intravenous adenosine. Potential drivers (PDs) were defined as focal or rotational activations completing ≥ 1.5 revolutions. Distribution of PDs was assessed using an 18 segment biatrial model. Results 46 patients were enrolled. Mean age was 63.4 ± 9.8 years with 33 (72%) being male. There was no significant difference in the number of PDs recorded at baseline compared to adenosine (42.1 ± 15.2 vs 40.4 ± 13.0; p = 0.417), nor in the number of segments harbouring PDs, (13 (11–14) vs 12 (10–14); p = 0.169). There was a significantly higher percentage of PDs that were focal in the adenosine maps (36.2 ± 15.2 vs 32.2 ± 14.4; p < 0.001). There was a significant shortening of CL in the adenosine maps compared to baseline which was more marked in the right atrium than left atrium (176.7 ± 34.7 vs 149.9 ± 27.7 ms; p < 0.001 and 165.6 ± 31.7 vs 148.3 ± 28.4 ms; p = 0.003). Conclusion Adenosine led to a small but significant shortening of CL which was more marked in the right than left atrium and may relate to shortening of refractory periods rather than an increase in driver burden or distribution. Registered on Clinicaltrials.gov: NCT03394404.


2003 ◽  
Vol 285 (5) ◽  
pp. H1837-H1848 ◽  
Author(s):  
Alan E. Lomax ◽  
Colleen S. Kondo ◽  
Wayne R. Giles

Consistent differences in K+ currents in left and right atria of adult mouse hearts have been identified by the application of current- and voltage-clamp protocols to isolated single myocytes. Left atrial myocytes had a significantly ( P < 0.05) larger peak outward K+ current density than myocytes from the right atrium. Detailed analysis revealed that this difference was due to the rapidly activating sustained K+ current, which is inhibited by 100 μM 4-aminopyridine (4-AP); this current was almost three times larger in the left atrium than in the right atrium. Accordingly, 100 μM 4-AP caused a significantly ( P < 0.05) larger increase in action potential duration in left than in right atrial myocytes. Inward rectifier K+ current density was also significantly ( P < 0.05) larger in left atrial myocytes. There was no difference in the voltage-dependent L-type Ca2+ current between left and right atria. As expected from this voltage-clamp data, the duration of action potentials recorded from single myocytes was significantly ( P < 0.05) shorter in myocytes from left atria, and left atrial tissue was found to have a significantly ( P < 0.05) shorter effective refractory period than right atrial tissue. These results reveal similarities between mice and other mammalian species where the left atrium repolarizes more quickly than the right, and provide new insight into cellular electrophysiological mechanisms responsible for this difference. These findings, and previous results, suggest that the atria of adult mice may be a suitable model for detailed studies of atrial electrophysiology and pharmacology under control conditions and in the context of induced atrial rhythm disturbances.


1994 ◽  
Vol 186 (1) ◽  
pp. 109-126 ◽  
Author(s):  
J. Hicks ◽  
S. Comeau

Two principal hypotheses account for intracardiac shunting in reptiles. The ‘pressure shunting’ hypothesis proposes that there is no fuctional separation between the ventricular cava during systole. The ‘washout shunting’ hypothesis suggests that the cavum pulmonale is functionally separated from the rest of the ventricle during systole. The purpose of this study was to test the two principal hypotheses in a turtle, Pseudemys scripta, after inducing a right-to-left shunt by electrical stimulation of the vagus nerve. Animals were anaesthetized with sodium pentobarbital (30–40 mg kg-1), tracheotomized and mechanically ventilated. Two experimental groups were used. Both groups had the right and left cervical vagi exposed and sectioned and silver bipolar electrodes were attached for electrical stimulation. In addition, cardiac function was evaluated by determining the pulmonary blood flow, pulmonary arterial pressure, peak systolic pressure in the cavum pulmonale, central arterial pressure, pulmonary vascular resistance and heart rate. In group I, hydrogen electrodes were inserted into the right aorta, the left aorta and the pulmonary artery. Hydrogen, dissolved in saline, was infused into the left atrium, jugular vein and cavum pulmonale. Blood flow from these sites was deduced from detection of a H2 signal in the right and left aortae and the pulmonary artery. In group II, catheters were inserted in the left and right atria and aortae for the measurement of blood gases. For both groups, the protocol consisted of control periods and periods of electrical stimulation of the efferent and afferent ends of the vagus nerve. During the control periods, infusion of a H2 solution into either the left atrium or the jugular vein resulted in the detection of H2 in the right and left aortae and the pulmonary artery. This suggested that both right-to-left and left-to-right intracardiac shunts were present. H2 infused into the cavum pulmonale was always detected in the pulmonary artery but never in the left or right aortae. During stimulation of the right vagal efferents, a bradycardia developed (heart rate declined by 65 %), pulmonary blood flow was reduced by 73 % and pulmonary vascular resistance increased by 158 %. This was accompanied by a reduction in the PO2 of both the right and left aortae, although the PO2 of the left and right atria remained constant. Under these conditions, H2 infused into the jugular vein and the left atrium was detected in the right and left aortae and the pulmonary artery of all animals studied. Infusion of H2 into the cavum pulmonale was detected in the right and left aortae in only two animals. The results supported the washout mechanism for right-to-left intracardiac shunting.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sanda Iacobas ◽  
Bogdan Amuzescu ◽  
Dumitru A. Iacobas

AbstractMyocardium transcriptomes of left and right atria and ventricles from four adult male C57Bl/6j mice were profiled with Agilent microarrays to identify the differences responsible for the distinct functional roles of the four heart chambers. Female mice were not investigated owing to their transcriptome dependence on the estrous cycle phase. Out of the quantified 16,886 unigenes, 15.76% on the left side and 16.5% on the right side exhibited differential expression between the atrium and the ventricle, while 5.8% of genes were differently expressed between the two atria and only 1.2% between the two ventricles. The study revealed also chamber differences in gene expression control and coordination. We analyzed ion channels and transporters, and genes within the cardiac muscle contraction, oxidative phosphorylation, glycolysis/gluconeogenesis, calcium and adrenergic signaling pathways. Interestingly, while expression of Ank2 oscillates in phase with all 27 quantified binding partners in the left ventricle, the percentage of in-phase oscillating partners of Ank2 is 15% and 37% in the left and right atria and 74% in the right ventricle. The analysis indicated high interventricular synchrony of the ion channels expressions and the substantially lower synchrony between the two atria and between the atrium and the ventricle from the same side.


2020 ◽  
Vol 100 (4) ◽  
pp. 657-664
Author(s):  
Jiuxiu Ji ◽  
Taihua Jin ◽  
Rui Zhang ◽  
Angang Lou ◽  
Yingying Chen ◽  
...  

Yanbian yellow cattle breeding is limited by its slow growth. We previously found that the miRNA miR-6523a is differentially expressed between Yanbian yellow cattle and Han Yan cattle, which differ in growth characteristics. In this study, we evaluated the effects of miR-6523a on growth hormone (GH) secretion in pituitary cells of Yanbian yellow cattle. Bioinformatics analyses using TargetScan and RNAhybrid, as well as dual luciferase reporter assays, showed that miR-6523a targets the 3′ untranslated region of somatostatin receptor 5 (SSTR5). We further found that the mRNA and protein expression levels of GH in pituitary cells were significantly higher in cells treated with miR-6523a mimic than in the control group (P = 0.0082 and P = 0.0069). The GH mRNA and protein expression levels were lower in cells treated with miR-6523a inhibitor than in the control group, but the difference was not significant (P = 0.064 and P = 0.089). SSTR5 mRNA and protein levels were inhibited by miR-6523a mimic compared with the control group (P = 0.0024 and P = 0.0028) and were elevated slightly by miR-6523a inhibitor (P = 0.093 and P = 0.091). These results prove that miR-6523a regulates GH secretion in pituitary cells by SSTR5. More broadly, these findings provide a basis for studies of the roles of miRNAs in animal growth and development.


1988 ◽  
Vol 255 (3) ◽  
pp. H503-H513 ◽  
Author(s):  
R. B. Schuessler ◽  
T. E. Canavan ◽  
J. P. Boineau ◽  
J. L. Cox

In open-chest dogs, blood pressure was regulated by titrating doses of phenylephrine and nitroprusside to determine its effect on heart rate and pacemaker location. Changes in blood pressure correlated with changes in heart rate (r = 0.86). Activation time mapping demonstrated multicentric atrial activation, with a site of origin-rate relationship. The fastest pacemakers were located in the most cranial regions and slowest in the most caudal areas. In this chloralose-morphine anesthetized model, autonomic blockade with atropine and propranolol suggests that acute baroreflex-induced changes in heart rate were mediated exclusively by either increased sympathetic or parasympathetic tone and were not associated with inhibition of the opposite system. Division of right and left thoracic cardiac nerves indicated the left sympathetics participated in the baroreflex in 50% of the animals and the left parasympathetics in 90% of the animals. Both the right sympathetics and parasympathetics were active in the baroreflex in all animals. The data demonstrate that physiological heart rate response is regulated through an extensive system of right atrial pacemakers modulated by both left and right efferent cardiac nerves.


Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4203 ◽  
Author(s):  
Lei ◽  
Gao ◽  
Feng ◽  
Huang ◽  
Bian ◽  
...  

Endogenous formaldehyde is generated as a normal metabolite via bio-catalysis of γ-glutamyl transpeptidase (GGT) and L-cysteine sulfoxide lyase (C-S lyase) during the growth and development of Lentinula edodes. In this study, we investigated the mRNA and protein expression levels, the activities of GGT and C-S lyase, and the endogenous formaldehyde content in L. edodes at different growth stages. With the growth of L. edodes, a decrease was found in the mRNA and protein expression levels of GGT, while an increase was observed in the mRNA and protein expression levels of C-S lyase as well as the activities of GGT and C-S lyase. Our results revealed for the first time a positive relationship of formaldehyde content with the expression levels of Csl (encoding Lecsl) and Lecsl (C-S lyase protein of Lentinula edodes) as well as the enzyme activities of C-S lyase and GGT during the growth of L. edodes. This research provided a molecular basis for understanding and controlling the endogenous formaldehyde formation in Lentinula edodes in the process of growth.


2020 ◽  
Vol 103 (3) ◽  
pp. 608-619
Author(s):  
Ping Zhong ◽  
Jin Liu ◽  
Hong Li ◽  
Senbin Lin ◽  
Lingfeng Zeng ◽  
...  

Abstract This study aimed to investigate whether cadmium (Cd) cytotoxicity in rat ovarian granulosa cells (OGCs) is mediated through apoptosis or autophagy and to determine the role of microRNAs (miRNAs) in Cd cytotoxicity. To test this hypothesis, rat OGCs were exposed to 0, 10, and 20 μM CdCl2 in vitro. As the Cd concentration increased, OGC apoptosis increased. In addition, Cd promoted apoptosis by decreasing the mRNA and protein expression levels of inhibition of B-cell lymphoma 2 (Bcl2). However, under our experimental conditions, no autophagic changes in rat OGCs were observed, and the mRNA and protein expression levels of the autophagic markers microtubule-associated protein 1 light chain 3 alpha (Map1lc3b) and Beclin1 (Becn1) were not changed. Microarray chip analysis, miRNA screening, and bioinformatics approaches were used to further explore the roles of apoptosis regulation-related miRNAs. In total, 19 miRNAs putatively related to Cd-induced apoptosis in rat OGCs were identified. Notably, miR-204-5p, which may target Bcl2, was identified. Then, rat OGCs were cultured in vitro and used to construct the miR-204-5p-knockdown cell line LV2-short hairpin RNA (shRNA). LV2-shRNA cells were exposed to 20 μM Cd for 12 h, and the mRNA and protein expression levels of Bcl2 were increased. Our findings suggest that Cd is cytotoxic to rat OGCs, and mitochondrial apoptosis rather than autophagy mediates Cd-induced damage to OGCs. Cd also affects apoptosis-related miRNAs, and the underlying apoptotic mechanism may involve the Bcl2 gene.


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