Role of cytosolic calcium diffusion in cardiac purkinje cells

2016 ◽  
Author(s):  
Bijay Limbu ◽  
Kushal Shah ◽  
Makarand Deo
Keyword(s):  
Purkinje Cells ◽  
Cytosolic Calcium ◽  
Cardiac Purkinje Cells ◽  
Calcium Diffusion

scholarly journals Role of Cytosolic Calcium Diffusion in Murine Cardiac Purkinje Cells

2016 ◽  
Vol 10s1 ◽  
pp. CMC.S39705
Author(s):  
Bijay Limbu ◽  
Kushal Shah ◽  
Seth H. Weinberg ◽  
Makarand Deo
Keyword(s):  
Purkinje Cells ◽  
Ventricular Myocytes ◽  
Ionic Current ◽  
Cytosolic Calcium ◽  
Diffusion Waves ◽  
Cardiac Purkinje Cells ◽  
Calcium Diffusion ◽  
Intracellular Ca ◽  
Diffusion Rates

Cardiac Purkinje cells (PCs) are morphologically and electrophysiologically different from ventricular myocytes and, importantly, exhibit distinct calcium (Ca2+) homeostasis. Recent studies suggest that PCs are more susceptible to action potential (AP) abnormalities than ventricular myocytes; however, the exact mechanisms are poorly understood. In this study, we utilized a detailed biophysical mathematical model of a murine PC to systematically examine the role of cytosolic Ca2+ diffusion in shaping the AP in PCs. A biphasic spatiotemporal Ca2+ diffusion process, as recorded experimentally, was implemented in the model. In this study, we investigated the role of cytosolic Ca2+ dynamics on AP and ionic current properties by varying the effective Ca2+ diffusion rate. It was observed that AP morphology, specifically the plateau, was affected due to changes in the intracellular Ca2+ dynamics. Elevated Ca2+ concentration in the sarcolemmal region activated inward sodium-Ca2+ exchanger (NCX) current, resulting in a prolongation of the AP plateau at faster diffusion rates. Artificially clamping the NCX current to control values completely reversed the alterations in the AP plateau, thus confirming the role of NCX in modifying the AP morphology. Our results demonstrate that cytosolic Ca2+ diffusion waves play a significant role in shaping APs of PCs and could provide mechanistic insights in the increased arrhythmogeneity of PCs.

Role of Cytosolic Calcium Diffusion and Sarcolemmal T-Type Calcium Current in Triggered Activity in Purkinje Cells: A Simulation Study

Heart Rhythm ◽  
2011 ◽  
Vol 8 (11) ◽  
pp. 1821
Author(s):  
M. Deo ◽  
S.V. Pandit ◽  
R. Vaidyanathan ◽  
R. OConnell ◽  
M. Milstein ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Simulation Study ◽  
Calcium Current ◽  
Cytosolic Calcium ◽  
Triggered Activity ◽  
Calcium Diffusion

Slow delayed rectifier current and repolarization in canine cardiac Purkinje cells

2001 ◽  
Vol 280 (3) ◽  
pp. H1075-H1080 ◽  
Author(s):  
Wei Han ◽  
Zhiguo Wang ◽  
Stanley Nattel
Keyword(s):  
Purkinje Cells ◽  
Voltage Dependence ◽  
Delayed Rectifier ◽  
Adrenergic Stimulation ◽  
Early Afterdepolarizations ◽  
Voltage Range ◽  
Delayed Rectifier Current ◽  
Whole Cell Patch Clamp ◽  
Cardiac Purkinje Cells

Although cardiac Purkinje cells (PCs) are believed to be the source of early afterdepolarizations generating ventricular tachyarrhythmias in long Q-T syndromes (LQTS), the ionic determinants of PC repolarization are incompletely known. To evaluate the role of the slow delayed rectifier current ( I Ks) in PC repolarization, we studied PCs from canine ventricular false tendons with whole cell patch clamp (37°C). Typical I Ks voltage- and time-dependent properties were noted. Isoproterenol enhanced I Ks in a concentration-dependent fashion (EC50 ∼ 30 nM), negatively shifted I Ks activation voltage dependence, and accelerated I Ks activation. Block of I Ks with 293B did not alter PC action potential duration (APD) in the absence of isoproterenol; however, in the presence of isoproterenol, 293B significantly prolonged APD. We conclude that, without β-adrenergic stimulation, I Ks contributes little to PC repolarization; however, β-adrenergic stimulation increases the contribution of I Ks by increasing current amplitude, accelerating I Ks activation, and shifting activation voltage toward the PC plateau voltage range. I Ks may therefore provide an important “braking” function to limit PC APD prolongation in the presence of β-adrenergic stimulation.

scholarly journals Ryanodine receptor gating controls generation of diastolic calcium waves in cardiac myocytes

2015 ◽  
Vol 145 (6) ◽  
pp. 489-511 ◽  
Author(s):  
Pavol Petrovič ◽  
Ivan Valent ◽  
Elena Cocherová ◽  
Jana Pavelková ◽  
Alexandra Zahradníková
Keyword(s):  
Ryanodine Receptor ◽  
Calcium Sensitivity ◽  
Cytosolic Calcium ◽  
Calcium Waves ◽  
Calcium Sparks ◽  
Calcium Spark ◽  
Gating Model ◽  
Calcium Diffusion ◽  
Confocal Scanning ◽  
Deterministic Description

The role of cardiac ryanodine receptor (RyR) gating in the initiation and propagation of calcium waves was investigated using a mathematical model comprising a stochastic description of RyR gating and a deterministic description of calcium diffusion and sequestration. We used a one-dimensional array of equidistantly spaced RyR clusters, representing the confocal scanning line, to simulate the formation of calcium sparks. Our model provided an excellent description of the calcium dependence of the frequency of diastolic calcium sparks and of the increased tendency for the production of calcium waves after a decrease in cytosolic calcium buffering. We developed a hypothesis relating changes in the propensity to form calcium waves to changes of RyR gating and tested it by simulation. With a realistic RyR gating model, increased ability of RyR to be activated by Ca2+ strongly increased the propensity for generation of calcium waves at low (0.05–0.1-µM) calcium concentrations but only slightly at high (0.2–0.4-µM) calcium concentrations. Changes in RyR gating altered calcium wave formation by changing the calcium sensitivity of spontaneous calcium spark activation and/or the average number of open RyRs in spontaneous calcium sparks. Gating changes that did not affect RyR activation by Ca2+ had only a weak effect on the propensity to form calcium waves, even if they strongly increased calcium spark frequency. Calcium waves induced by modulating the properties of the RyR activation site could be suppressed by inhibiting the spontaneous opening of the RyR. These data can explain the increased tendency for production of calcium waves under conditions when RyR gating is altered in cardiac diseases.

scholarly journals Role of Ca2+ in Mediating Plant Responses to Extracellular ATP and ADP

2018 ◽  
Vol 19 (11) ◽  
pp. 3590 ◽  
Author(s):  
Greg Clark ◽  
Stanley Roux
Keyword(s):  
Cytosolic Calcium ◽  
Defense Responses ◽  
Receptor Activation ◽  
Extracellular Atp ◽  
Extracellular Nucleotides ◽  
Nucleoside Triphosphate ◽  
Plant Responses ◽  
Downstream Signaling ◽  
Nucleoside Triphosphate Diphosphohydrolase

Among the most recently discovered chemical regulators of plant growth and development are extracellular nucleotides, especially extracellular ATP (eATP) and extracellular ADP (eADP). Plant cells release ATP into their extracellular matrix under a variety of different circumstances, and this eATP can then function as an agonist that binds to a specific receptor and induces signaling changes, the earliest of which is an increase in the concentration of cytosolic calcium ([Ca2+]cyt). This initial change is then amplified into downstream-signaling changes that include increased levels of reactive oxygen species and nitric oxide, which ultimately lead to major changes in the growth rate, defense responses, and leaf stomatal apertures of plants. This review presents and discusses the evidence that links receptor activation to increased [Ca2+]cyt and, ultimately, to growth and diverse adaptive changes in plant development. It also discusses the evidence that increased [Ca2+]cyt also enhances the activity of apyrase (nucleoside triphosphate diphosphohydrolase) enzymes that function in multiple subcellular locales to hydrolyze ATP and ADP, and thus limit or terminate the effects of these potent regulators.

scholarly journals Mice With Monoallelic GNAO1 Loss Exhibit Reduced Inhibitory Synaptic Input To Cerebellar Purkinje Cells

2021 ◽  
Author(s):  
Huijie Feng ◽  
Yukun Yuan ◽  
Michael R Williams ◽  
Alex Roy ◽  
Jeffrey Leipprandt ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Purkinje Cells ◽  
Gabab Receptor ◽  
Molecular Layer ◽  
Loss Of Function ◽  
Whole Cell Patch Clamp ◽  
The Difference ◽  
G Protein Alpha Subunit ◽  
Cerebellar Purkinje Cells

GNAO1 encodes Gαo, a heterotrimeric G protein alpha subunit in the Gi/o family. In this report, we used a Gnao1 mouse model G203R previously described as a gain-of-function Gnao1 mutant with movement abnormalities and enhanced seizure susceptibility. Here, we report an unexpected second mutation resulting in a loss-of-function Gαo protein and describe alterations in central synaptic transmission. Whole cell patch clamp recordings from Purkinje cells (PCs) in acute cerebellar slices from Gnao1 mutant mice showed significantly lower frequencies of spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) compared to WT mice. There was no significant change in sEPSCs or mEPSCs. Whereas mIPSC frequency was reduced, mIPSC amplitudes were not affected, suggesting a presynaptic mechanism of action. A modest decrease in the number of molecular layer interneurons was insufficient to explain the magnitude of IPSC suppression. Paradoxically, Gi/o inhibitors (pertussis toxin), enhanced the mutant-suppressed mIPSC frequency and eliminated the difference between WT and Gnao1 mice. While GABAB receptor regulates mIPSCs, neither agonists nor antagonists of this receptor altered function in the mutant mouse PCs. This study is the first electrophysiological investigation of the role of Gi/o protein in cerebellar synaptic transmission using an animal model with a loss-of-function Gi/o protein.

scholarly journals The Effect of Induced Diabetes Mellitus on the Cerebellar Cortex of Adult Male Rat and the Possible Protective Role of Oxymatrine: A Histological, Immunohistochemical and Biochemical Study

2021 ◽  
Author(s):  
Amany Mohamed Shalaby ◽  
Adel Mohamed Aboregela ◽  
Mohamed Ali Alabiad ◽  
Mona Tayssir Sadek
Keyword(s):  
Diabetes Mellitus ◽  
Purkinje Cells ◽  
Cerebellar Cortex ◽  
Adult Male ◽  
Protective Role ◽  
Diabetic Rats ◽  
Male Rats ◽  
Group I ◽  
Group Ii

Abstract Diabetes mellitus (DM) represents a widespread metabolic disease with a well-known neurotoxicity in both central and peripheral nervous systems. Oxymatrine is a traditional Chinese herbal medicine that has various pharmacological activities including; anti-oxidant, anti-apoptotic and anti-inflammatory potentials. The present work aimed to study the impact of diabetes mellitus on the cerebellar cortex of adult male albino rat and to evaluate the potential protective role of oxymatrine using different histological methods. Fifty-five adult male rats were randomly divided into three groups: group I served as control, group II was given oxymatrine (80 mg/kg/day) orally for 8 weeks and group III was given a single dose of streptozotocin (50mg/kg) intaperitoneally to induce diabetes. Then diabetic rats were subdivided into two subgroups: subgroup IIIa that received no additional treatment and subgroup IIIb that received oxymatrine similar to group II. The diabetic group revealed numerous changes in the Purkinje cell layer in the form of multilayer arrangement of Purkinje cells, shrunken cells with deeply stained nuclei as well as focal loss of the Purkinje cells. A significant increment in GFAP and synaptophysin expression was reported. Transmission electron microscopy showed irregularity and splitting of myelin sheaths in the molecular layer, dark shrunken Purkinje cells with ill-defined nuclei, dilated Golgi saccules and dense granule cells with irregular nuclear outlines in the granular layer. In contrast, these changes were less evident in diabetic rats that received oxymatrine. In conclusion, Oxymatrine could protect the cerebellar cortex against changes induced by DM.

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