REGULATION OF CARDIAC EXCITATION-CONTRACTION COUPLING: A CELLULAR UPDATE

2003 ◽  
Vol 27 (4) ◽  
pp. 192-200 ◽  
Author(s):  
Donna H. Korzick
Keyword(s):  
Nitric Oxide ◽  
Intracellular Signaling ◽  
Cardiac Performance ◽  
Functional Responses ◽  
Signaling Complex ◽  
Ec Coupling ◽  
Intracellular Ca ◽  
New Ideas ◽  
Cardiac Excitation

The primary purpose of this paper is to present a basic overview of some “relatively” new ideas related to the regulation of cardiac performance and underlying excitation-contraction (EC) coupling that have yet to be incorporated to textbooks currently used for introductory graduate-level physiology courses. Within the context of cardiac EC coupling, this review incorporates information on microdomains and local control theory, with particular emphasis on the role of Ca2+ sparks as a key regulatory component of ventricular myocyte contraction dynamics. Recent information pertaining to Ca2+ release mechanisms specific to the sarcoplasmic reticulum is also presented, as well as the idea of the ryanodine receptor as a macromolecular signaling complex. Because of the potential relationship to maladaptive functional responses under conditions of cardiovascular pathology, the regulatory role of cardiac adrenergic and additional G protein-coupled receptors known to regulate cardiac function is included, and fundamental concepts related to intracellular signaling are discussed. Finally, information on the roles of vascular and cardiac nitric oxide as an important regulator of cardiac performance is included to allow students to begin to think about the ubiquitous role of nitric oxide in the regulation of the cardiovascular system. An important point of emphasis is that whole organ cardiac dynamics can be traced back to the cellular events regulating intracellular Ca2+ homeostasis and as such provides an important conceptual framework from which the students can begin to think about whole organ physiology in health and disease.

scholarly journals From syncitium to regulated pump: a cardiac muscle cellular update

2011 ◽  
Vol 35 (1) ◽  
pp. 22-27 ◽  
Author(s):  
Donna H. Korzick
Keyword(s):  
Cardiac Muscle ◽  
Intracellular Signaling ◽  
Ventricular Myocytes ◽  
Cellular Events ◽  
Intracellular Ca ◽  
Health And Disease ◽  
Cardiac Excitation ◽  
And Function ◽  
Cardiac Automaticity

The primary purpose of this article is to present a basic overview of some key teaching concepts that should be considered for inclusion in an six- to eight-lecture introductory block on the regulation of cardiac performance for graduate students. Within the context of cardiac excitation-contraction coupling, this review incorporates information on Ca2+ microdomains and local control theory, with particular emphasis on the role of Ca2+ sparks as a key regulatory component of ventricular myocyte contraction dynamics. Recent information pertaining to local Ca2+ cycling in sinoatrial nodal cells (SANCs) as a mechanism underlying cardiac automaticity is also presented as part of the recently described coupled-clock pacemaker system. The details of this regulation are emerging; however, the notion that the sequestration and release of Ca2+ from internal stores in SANCs (similar to that observed in ventricular myocytes) regulates the rhythmic excitation of the heart (i.e., membrane ion channels) is an important advancement in this area. The regulatory role of cardiac adrenergic receptors on cardiac rate and function is also included, and fundamental concepts related to intracellular signaling are discussed. An important point of emphasis is that whole organ cardiac dynamics can be traced back to cellular events regulating intracellular Ca2+ homeostasis and, as such, provides an important conceptual framework from which students can begin to think about whole organ physiology in health and disease. Greater synchrony of Ca2+-regulatory mechanisms between ventricular and pacemaker cells should enhance student comprehension of complex regulatory phenomenon in cardiac muscle.

scholarly journals Cardiac performance in Salmo salar with infectious salmon anaemia (ISA): putative role of nitric oxide

2002 ◽  
Vol 52 ◽  
pp. 11-20 ◽  
Author(s):  
A Gattuso ◽  
R Mazza ◽  
S Imbrogno ◽  
A Sverdrup ◽  
B Tota ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Salmo Salar ◽  
Cardiac Performance ◽  
Putative Role ◽  
Infectious Salmon Anaemia

Ryanodine receptor function in newborn rat heart

2005 ◽  
Vol 288 (5) ◽  
pp. H2527-H2540 ◽  
Author(s):  
Claudia G. Pérez ◽  
Julio A. Copello ◽  
Yanxia Li ◽  
Kimberly L. Karko ◽  
Leticia Gómez ◽  
...  
Keyword(s):  
Lipid Bilayers ◽  
Ryanodine Receptor ◽  
Functional Properties ◽  
Rat Heart ◽  
Single Channel ◽  
Binding Assays ◽  
Adult Rats ◽  
Intracellular Ca ◽  
Cardiac Excitation

The role of ryanodine receptor (RyR) in cardiac excitation-contraction (E-C) coupling in newborns (NB) is not completely understood. To determine whether RyR functional properties change during development, we evaluated cellular distribution and functionality of sarcoplasmic reticulum (SR) in NB rats. Sarcomeric arrangement of immunostained SR Ca2+-ATPase (SERCA2a) and the presence of sizeable caffeine-induced Ca2+ transients demonstrated that functional SR exists in NB. E-C coupling properties were then defined in NB and compared with those in adult rats (AD). Ca2+ transients in NB reflected predominantly sarcolemmal Ca2+ entry, whereas the RyR-mediated component was ∼13%. Finally, the RyR density and functional properties at the single-channel level in NB were compared with those in AD. Ligand binding assays revealed that in NB, RyR density can be up to 36% of that found in AD, suggesting that some RyRs do not contribute to the Ca2+ transient. To test the hypothesis that RyR functional properties change during development, we incorporated single RyRs into lipid bilayers. Our results show that permeation and gating kinetics of NB RyRs are identical to those of AD. Also, endogenous ligands had similar effects on NB and AD RyRs: sigmoidal Ca2+ dependence, stronger Mg2+-induced inhibition at low cytoplasmic Ca2+ concentrations, comparable ATP-activating potency, and caffeine sensitivity. These observations indicate that NB rat heart contains fully functional RyRs and that the smaller contribution of RyR-mediated Ca2+ release to the intracellular Ca2+ transient in NB is not due to different single RyR channel properties or to the absence of functional intracellular Ca2+ stores.

scholarly journals Role of Oxidative Stress and Mitochondrial Dysfunction in Sepsis and Potential Therapies

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Konstantinos Mantzarlis ◽  
Vasiliki Tsolaki ◽  
Epaminondas Zakynthinos
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Intensive Care ◽  
Vitamin C ◽  
Causes Of Death ◽  
Redox Balance ◽  
Cardiac Performance ◽  
Efficiency Evaluation ◽  
Permeability Impairment

Sepsis is one of the most important causes of death in intensive care units. Despite the fact that sepsis pathogenesis remains obscure, there is increasing evidence that oxidants and antioxidants play a key role. The imbalance of the abovementioned substances in favor of oxidants is called oxidative stress, and it contributes to sepsis process. The most important consequences are vascular permeability impairment, decreased cardiac performance, and mitochondrial malfunction leading to impaired respiration. Nitric oxide is perhaps the most important and well-studied oxidant. Selenium, vitamin C, and 3N-acetylcysteine among others are potential therapies for the restoration of redox balance in sepsis. Results from recent studies are promising, but there is a need for more human studies in a clinical setting for safety and efficiency evaluation.

Characterizing voltage-dependent Ca2+ channels coupled to VIP release and NO synthesis in enteric synaptosomes

2002 ◽  
Vol 283 (5) ◽  
pp. G1027-G1034 ◽  
Author(s):  
M. Kurjak ◽  
A. Sennefelder ◽  
M. Aigner ◽  
V. Schusdziarra ◽  
H. D. Allescher
Keyword(s):  
Nitric Oxide ◽  
No Synthase ◽  
Channel Blockers ◽  
Voltage Dependent ◽  
Intracellular Ca ◽  
P Type ◽  
Ca2 Channels

In enteric synaptosomes of the rat, the role of voltage-dependent Ca2+channels in K+-induced VIP release and nitric oxide (NO) synthesis was investigated. Basal VIP release was 39 ± 4 pg/mg, and cofactor-substituted NO synthase activity was 7.0 ± 0.8 fmol · mg−1 · min−1. K+ depolarization (65 mM) stimulated VIP release Ca2+ dependently (basal, 100%; K+, 172.2 ± 16.2%; P < 0.05, n = 5). K+-stimulated VIP release was reduced by blockers of the P-type (ω-agatoxin-IVA, 3 × 10−8 M) and N-type (ω-conotoxin-GVIA, 10−6 M) Ca2+ channels by ∼50 and 25%, respectively, but not by blockers of the L-type (isradipine, 10−8 M), Q-type (ω-conotoxin-MVIIC, 10−6 M), or T-type (Ni2+, 10−6 M) Ca2+ channels. In contrast, NO synthesis was suppressed by ω-agatoxin-IVA, ω-conotoxin-GVIA, and isradipine by ∼79, 70, and 70%, respectively, whereas Ni2+ and ω-conotoxin-MVIIC had no effect. These findings are suggestive of a coupling of depolarization-induced VIP release primarily to the P- and N-type Ca2+ channels, whereas NO synthesis is presumably dependent on Ca2+ influx not only via the P- and N- but also via the L-type Ca2+ channel. In contrast, none of the Ca2+ channel blockers affected VIP release evoked by exogenous NO, suggesting that NO induces VIP secretion by a different mechanism, presumably involving intracellular Ca2+ stores.

Mechanisms of endothelial P2Y1- and P2Y2-mediated vasodilatation involve differential [Ca2+]i responses

2001 ◽  
Vol 281 (4) ◽  
pp. H1759-H1766 ◽  
Author(s):  
Sean P. Marrelli
Keyword(s):  
Nitric Oxide ◽  
Simultaneous Measurement ◽  
Cerebral Arteries ◽  
No Synthase ◽  
Fura 2 ◽  
Middle Cerebral Arteries ◽  
Intracellular Ca ◽  
The Difference ◽  
Stimulation Of

The present study was designed to evaluate the role of endothelial intracellular Ca2+ concentration ([Ca2+]i) in the difference between P2Y1- and P2Y2-mediated vasodilatations in cerebral arteries. Rat middle cerebral arteries were cannulated, pressurized, and luminally perfused. The endothelium was selectively loaded with fura 2, a fluorescent Ca2+indicator, for simultaneous measurement of endothelial [Ca2+]i and diameter. Luminal administration of 2-methylthioadenosine 5′-triphosphate (2-MeS-ATP), an endothelial P2Y1 agonist, resulted in purely nitric oxide (NO)-dependent dilation and [Ca2+]i increases up to ∼300 nM (resting [Ca2+]i = 145 nM). UTP, an endothelial P2Y2 agonist, resulted in dilations that were both endothelium-derived hyperpolarizing factor (EDHF)- and NO-dependent with [Ca2+]iincreases to >400 nM. In the presence of N G-nitro-l-arginine-indomethacin to inhibit NO synthase and cyclooxygenase, UTP resulted in an EDHF-dependent dilation alone. The [Ca2+]ithreshold for NO-dependent dilation was 220 vs. 340 nM for EDHF. In summary, the differences in the mechanism of vasodilatation resulting from stimulation of endothelial P2Y1 and P2Y2purinoceptors result in part from differential [Ca2+]i responses. Consistent with this finding, these studies also demonstrate a higher [Ca2+]i threshold for EDHF-dependent responses compared with NO.

Nitric oxide induces [Ca2+]i oscillations in pituitary GH3 cells: involvement of IDR and ERG K+ currents

2006 ◽  
Vol 290 (1) ◽  
pp. C233-C243 ◽  
Author(s):  
Agnese Secondo ◽  
Anna Pannaccione ◽  
Mauro Cataldi ◽  
Rossana Sirabella ◽  
Luigi Formisano ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inhibitory Effect ◽  
Receptor Blocker ◽  
Gh3 Cells ◽  
No Donors ◽  
Quiescent Cells ◽  
Voltage Dependent ◽  
Intracellular Ca ◽  
Trisphosphate Receptor

The role of nitric oxide (NO) in the occurrence of intracellular Ca2+ concentration ([Ca2+]i) oscillations in pituitary GH3 cells was evaluated by studying the effect of increasing or decreasing endogenous NO synthesis with l-arginine and nitro-l-arginine methyl ester (l-NAME), respectively. When NO synthesis was blocked with l-NAME (1 mM) [Ca2+]i, oscillations disappeared in 68% of spontaneously active cells, whereas 41% of the quiescent cells showed [Ca2+]i oscillations in response to the NO synthase (NOS) substrate l-arginine (10 mM). This effect was reproduced by the NO donors NOC-18 and S-nitroso- N-acetylpenicillamine (SNAP). NOC-18 was ineffective in the presence of the L-type voltage-dependent Ca2+ channels (VDCC) blocker nimodipine (1 μM) or in Ca2+-free medium. Conversely, its effect was preserved when Ca2+ release from intracellular Ca2+ stores was inhibited either with the ryanodine-receptor blocker ryanodine (500 μM) or with the inositol 1,4,5-trisphosphate receptor blocker xestospongin C (3 μM). These results suggest that NO induces the appearance of [Ca2+]i oscillations by determining Ca2+ influx. Patch-clamp experiments excluded that NO acted directly on VDCC but suggested that NO determined membrane depolarization because of the inhibition of voltage-gated K+ channels. NOC-18 and SNAP caused a decrease in the amplitude of slow-inactivating ( IDR) and ether-à-go-go-related gene ( ERG) hyperpolarization-evoked, deactivating K+ currents. Similar results were obtained when GH3 cells were treated with l-arginine. The present study suggests that in GH3 cells, endogenous NO plays a permissive role for the occurrence of spontaneous [Ca2+]i oscillations through an inhibitory effect on IDR and on IERG.

The putative wnt receptor Xenopus frizzled-7 functions upstream of beta-catenin in vertebrate dorsoventral mesoderm patterning

Development ◽  
2000 ◽  
Vol 127 (9) ◽  
pp. 1981-1990 ◽  
Author(s):  
S. Sumanas ◽  
P. Strege ◽  
J. Heasman ◽  
S.C. Ekker
Keyword(s):  
Antisense Oligonucleotide ◽  
Intracellular Signaling ◽  
Target Genes ◽  
Cell Communication ◽  
Beta Catenin ◽  
Signaling Complex ◽  
Wnt Proteins ◽  
Mesoderm Specification ◽  
Mesoderm Patterning

We have isolated one member of the frizzled family of wnt receptors from Xenopus (Xfz7) to study the role of cell-cell communication in the establishment of the vertebrate axis. We demonstrate that this maternally encoded protein specifically synergizes with wnt proteins in ectopic axis induction. Embryos derived from oocytes depleted of maternal Xfz7 RNA by antisense oligonucleotide injection are deficient in dorsoanterior structures. Xfz7-depleted embryos are deficient in dorsal but not ventral mesoderm due to the reduced expression of the wnt target genes siamois, Xnr3 and goosecoid. These signaling defects can be restored by the addition of beta-catenin but not Xwnt8b. Xfz7 thus functions upstream of the known GSK-3/axin/beta-catenin intracellular signaling complex in vertebrate dorsoventral mesoderm specification.

scholarly journals Role of nitric oxide synthases polymorphism in the development of comorbidity of bronchial asthma and hypertension

2017 ◽  
Vol 98 (2) ◽  
pp. 226-232
Author(s):  
O M Uryas’ev ◽  
A V Shakhanov
Keyword(s):  
Nitric Oxide ◽  
Bronchial Asthma ◽  
Intracellular Signaling ◽  
Genetic Factors ◽  
Nitric Oxide Synthases ◽  
Response Factors ◽  
Humoral Immune ◽  
Mediators Of Inflammation ◽  
Genes Encoding

Present literature review highlights the current views on the role of genetic factors in the development of bronchial asthma and hypertension, indicates their role in the formation of comorbid pathology, draws attention to the role of nitric oxide and nitric oxide synthase genes in the pathogenesis. In recent years there has been increasing interest of researchers to the problem of comorbidity, in particular to a combination of asthma and hypertension. Genetic factors play a great role in pathogenesis of these diseases. Among genes that play role in development of asthma there are genes encoding antigen recognition factors and humoral immune response factors, genes encoding mediators of inflammation, chemokines and intercellular adhesion molecules, genes of receptors performing fixation of external ligand molecules on the target cell, genes of intracellular signaling molecules and transcription factors and a number of other genes. The pathogenesis of essential hypertension is associated with the genes of renin-angiotensin-aldosterone system and genes regulating endothelial status. The link between asthma and hypertension is nitric oxide, which is involved in many physiological processes, in particular, regulates vascular and respiratory tone. Polymorphism of nitric oxide synthases genes is able to violate its production in the organism and thus lead to the development of bronchial asthma and hypertension. Polymorphisms Glu298Asp, eNOS4a/b, and 786C/T of NOS3 gene are associated with development of hypertension. Polymorphisms of this gene had been studied in patients with bronchial asthma, and they have demonstrated their influence on the level of nitric oxide in patients. Thus, the NOS gene polymorphisms may participate in the formation of comorbidity of bronchial asthma and hypertension.

ROLE OF NITRIC OXIDE IN CARDIAC PERFORMANCE DURING EXPERIMENTAL ISCHEMIC CARDIAC ARREST AND REPERFUSION

2019 ◽  
Vol 70 (10) ◽  
pp. 669-688
Author(s):  
Faten Diab ◽  
Mahmoud Ayobe ◽  
Enas Abdel-Hady ◽  
Mohamed Abdel- Salam ◽  
Mohammed Othman
Keyword(s):  
Nitric Oxide ◽  
Cardiac Arrest ◽  
Cardiac Performance
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