scholarly journals Altered Calcium Handling and Ventricular Arrhythmias in Acute Ischemia

2016 ◽  
Vol 10s1 ◽  
pp. CMC.S39706 ◽  
Author(s):  
Peter Baumeister ◽  
T. Alexander Quinn
Keyword(s):  
Intracellular Calcium ◽  
Ventricular Arrhythmias ◽  
Calcium Concentration ◽  
Calcium Transient ◽  
Biochemical Properties ◽  
Calcium Handling ◽  
Acute Ischemia ◽  
Potential Contribution ◽  
Novel Targets ◽  
Ectopic Excitation

Acute ischemia results in deadly cardiac arrhythmias that are a major contributor to sudden cardiac death (SCD). The electrophysiological changes involved have been extensively studied, yet the mechanisms of ventricular arrhythmias during acute ischemia remain unclear. What is known is that during acute ischemia both focal (ectopic excitation) and nonfocal (reentry) arrhythmias occur, due to an interaction of altered electrical, mechanical, and biochemical properties of the myocardium. There is particular interest in the role that alterations in intracellular calcium handling, which cause changes in intracellular calcium concentration and to the calcium transient, play in ischemia-induced arrhythmias. In this review, we briefly summarize the known contributors to ventricular arrhythmias during acute ischemia, followed by an in-depth examination of the potential contribution of altered intracellular calcium handling, which may include novel targets for antiarrhythmic therapy.

Abstract 14727: Late Sodium Current Plays a Role in Ventricular Arrhythmias Associated With Increased Intracellular Calcium Concentration

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Xiaohong Wei ◽  
Yong Huo ◽  
Sihui Huang ◽  
Qiaomei Yang ◽  
Lu Ren ◽  
...  
Keyword(s):  
Intracellular Calcium ◽  
Ventricular Arrhythmias ◽  
Calcium Concentration ◽  
Sodium Current ◽  
Calcium Transient ◽  
Bay K 8644 ◽  
Intracellular Calcium Concentration ◽  
Polymorphic Ventricular Tachycardia ◽  
Late Sodium Current ◽  
Multiple Channel

Objective: An increase in intracellular calcium concentration is associated with the prolongation of action potential duration (APD) and polymorphic ventricular tachycardia (PVT). Recent studies indicated that late sodium current inhibitor is effective in preventing ventricular arrhythmias in patients with long QT syndrome 8. The objective of the study was to determine the role of late sodium current in calcium related ventricular arrhythmias. Methods: Hearts from New Zealand female rabbits were perfused in a Langendorff mode. The atrioventricular nodal area was thermally ablated to produce complete atrioventricular block, and then heart was paced at stated frequency. Multiple channel monophasic action potentials (MAP) and pseudo 12-lead electrocardiograms (ECGs) were recorded. Calcium transient and myocyte contraction were determined in rabbit ventricular myocytes. Results: Bay-K 8644 (10-300 nM) increased both epi- and endo- cardial MAPD90 of left ventricle in concentration dependent manners, from (176±6) to (222±13) ms, and (201±6) to (246±10) ms (n=15, p<0.05 vs control), respectively. In the presence of 1 nM ATX-II, Bay-K 8644 caused a greater prolongation of epi-MAPD90 which was increased from (182±6) to (342±21) ms (n=9, p<0.05 vs control). The prolongation of MAPD90 caused by Bay-K 8644 were reversed by 1 μM TTX in both absence and presence of ATX-II. Additionally, the incidence of PVT evoked by Bay-K 8644 was also greater in the presence compared to the absence of ATX-II. 200 nM Bay-K 8644 caused few arrhythmias in absence of ATX-II. In contrast, PVT occurred in 7/9 (77.78%) of hearts treated with 200 nM Bay-K 8644 in the presence of ATX-II. These arrhythmias could be abolished by 1 μM TTX in the continued presence of Bay-K 8644. TTX (1 μM) attenuated the increase by 200 nM Bay-K 8644 of intracellular calcium transient and myocyte contraction amplitude by 10.8% and 14.6%, respectively (n=6, p<0.05). Conclusion: Both endogenous and enhanced late sodium current contributes to the ventricular arrhythmias with increased intracellular calcium concentration. Inhibition of late sodium current may be effective in preventing or treating calcium overload-related ventricular arrhythmias and dysfunction of myocardial contraction.

Frequency-dependent acceleration of relaxation involves decreased myofilament calcium sensitivity

2007 ◽  
Vol 292 (5) ◽  
pp. H2212-H2219 ◽  
Author(s):  
Kenneth D. Varian ◽  
Paul M. L. Janssen
Keyword(s):  
Intracellular Calcium ◽  
Calcium Concentration ◽  
Troponin I ◽  
Zealand White Rabbit ◽  
Calcium Sensitivity ◽  
Intracellular Calcium Concentration ◽  
Calcium Handling ◽  
Force Frequency ◽  
Frequency Dependent ◽  
Myofilament Calcium Sensitivity

The force-frequency relationship is an intrinsic modulator of cardiac contractility and relaxation. Force of contraction increases with frequency, while simultaneously a frequency-dependent acceleration of relaxation occurs. While frequency dependency of calcium handling and sarcoplasmic reticulum calcium load have been well described, it remains unknown whether frequency-dependent changes in myofilament calcium sensitivity occur. We hypothesized that an increase in heart rate that results in acceleration of relaxation is accompanied by a proportional decrease in myofilament calcium sensitivity. To test our hypothesis, ultrathin right ventricular trabeculae were isolated from New Zealand White rabbit hearts and iontophorically loaded with the calcium indicator bis-fura 2. Twitch and intracellular calcium handling parameters were measured and showed a robust increase in twitch force, acceleration of relaxation, and rise in both diastolic and systolic intracellular calcium concentration with increased frequency. Steady-state force-intracellular calcium concentration relationships were measured at frequencies 1, 2, 3, and 4 Hz at 37°C using potassium-induced contractures. EC50 significantly and gradually increased with frequency, from 475 ± 64 nM at 1 Hz to 1,004 ± 142 nM at 4 Hz ( P < 0.05) and correlated with the corresponding changes in half relaxation time. No significant changes in maximal active force development or in the myofilament cooperativity coefficient were found. Myofilament protein phosphorylation was assessed using Pro-Q Diamond staining on protein gels of trabeculae frozen at either 1 or 4 Hz, revealing troponin I and myosin light chain-2 phosphorylation associated with the myofilament desensitization. We conclude that myofilament calcium sensitivity is substantially and significantly decreased at higher frequencies, playing a prominent role in frequency-dependent acceleration of relaxation.

Parathyroid hormone acutely elevates intracellular calcium in osteoblastlike cells

1987 ◽  
Vol 253 (1) ◽  
pp. E45-E51 ◽  
Author(s):  
I. R. Reid ◽  
R. Civitelli ◽  
L. R. Halstead ◽  
L. V. Avioli ◽  
K. A. Hruska
Keyword(s):  
Parathyroid Hormone ◽  
Intracellular Calcium ◽  
Calcium Concentration ◽  
Calcium Transient ◽  
Peak Height ◽  
Base Line ◽  
Osteosarcoma Cell ◽  
Cellular Processes ◽  
Osteoblastic Phenotype ◽  
Umr 106

Changes in cytoplasmic calcium concentration ([Ca2+]i) activate numerous cellular processes thus mediating the effects of a number of hormones, but whether this mechanism is involved in the activation of osteoblasts by parathyroid hormone (PTH) remains uncertain. To examine this question, [Ca2+]i has been measured in suspensions of UMR 106 cells, a rodent osteosarcoma cell line with an osteoblastic phenotype. Basal [Ca2+]i was 137 +/- 3.7 nM (n = 60) and after the addition of rat PTH-(1–34) [rPTH-(1-34)] there was a rapid, dose-related increase with return to base line within 1 min. Half-maximal stimulation was produced by 5 X 10(-8) M rPTH-(1-34). Complexing of intracellular calcium by EGTA addition immediately before that of rPTH did not affect the calcium transient; neither did MnCl2 (10(-4) M) nor diltiazem (10(-4) M). Verapamil (10(-5) M) reduced the [Ca2+]i peak height after rPTH to 0.48 +/- 0.14 of control (n = 7). 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoic acid and dantrolene both reduced the [Ca2+]i response to rPTH (0.65 +/- 0.08 and 0.29 +/- 0.13 of control, respectively). Forskolin (10(-6) and 10(-5) M) produced a slight [Ca2+]i transient smaller in amplitude than seen with PTH. It is concluded that PTH mobilizes an intracellular calcium pool in these osteoblastlike cells, and the predominant mechanism for this is independent of cAMP.

Intracellular calcium handling heterogeneities in intact guinea pig hearts

2004 ◽  
Vol 286 (2) ◽  
pp. H648-H656 ◽  
Author(s):  
Rodolphe P. Katra ◽  
Etienne Pruvot ◽  
Kenneth R. Laurita
Keyword(s):  
Guinea Pig ◽  
Intracellular Calcium ◽  
Calcium Release ◽  
Optical Mapping ◽  
Contractile Function ◽  
Calcium Transient ◽  
Calcium Transients ◽  
Calcium Handling ◽  
Excitation Light ◽  
Intact Heart

Regional heterogeneities of ventricular repolarizing currents and their role in arrhythmogenesis have received much attention; however, relatively little is known regarding heterogeneities of intracellular calcium handling. Because repolarization properties and contractile function are heterogeneous from base to apex of the intact heart, we hypothesize that calcium handling is also heterogeneous from base to apex. To test this hypothesis, we developed a novel ratiometric optical mapping system capable of measuring calcium fluorescence of indo-1 at two separate wavelengths from 256 sites simultaneously. With the use of intact Langendorff-perfused guinea pig hearts, ratiometric calcium transients were recorded under normal conditions and during administration of known inotropic agents. Ratiometric calcium transients were insensitive to changes in excitation light intensity and fluorescence over time. Under control conditions, calcium transient amplitude near the apex was significantly larger (60%, P < 0.01) compared with the base. In contrast, calcium transient duration was significantly longer (7.5%, P < 0.03) near the base compared with the apex. During isoproterenol (0.05 μM) and verapamil (2.5 μM) administration, ratiometric calcium transients accurately reflected changes in contractile function, and, the direction of base-to-apex heterogeneities remained unchanged compared with control. Ratiometric optical mapping techniques can be used to accurately quantify heterogeneities of calcium handling in the intact heart. Significant heterogeneities of calcium release and sequestration exist from base to apex of the intact heart. These heterogeneities are consistent with base-to-apex heterogeneities of contraction observed in the intact heart and may play a role in arrhythmogenesis under abnormal conditions.

scholarly journals Orientia tsutsugamushi Inhibits Apoptosis of Macrophages by Retarding Intracellular Calcium Release

2002 ◽  
Vol 70 (8) ◽  
pp. 4692-4696 ◽  
Author(s):  
Mee-Kyung Kim ◽  
Seung-Yong Seong ◽  
Ju-Young Seoh ◽  
Tae-Hee Han ◽  
Hyeon-Je Song ◽  
...  
Keyword(s):  
Intracellular Calcium ◽  
Calcium Concentration ◽  
Calcium Release ◽  
Cytosolic Calcium ◽  
Orientia Tsutsugamushi ◽  
Cytosolic Calcium Concentration ◽  
Infected Cells ◽  
Intracellular Calcium Release ◽  
Calcium Redistribution ◽  
In Cells

ABSTRACT Orientia tsutsugamushi shows both pro- and antiapoptotic activities in infected vertebrate cells. Apoptosis of THP-1 cells induced by beauvericin was inhibited by O. tsutsugamushi infection. Beauvericin-induced calcium redistribution was significantly reduced and retarded in cells infected with O. tsutsugamushi. Antiapoptotic activities of O. tsutsugamushi in infected cells are most probably due to inhibition of the increase in the cytosolic calcium concentration.

Effect of Small Increments in Plasma Calcium Concentration on the Responsiveness of Forearm Resistance Vessels to Verapamil in Normal Subjects

1984 ◽  
Vol 67 (6) ◽  
pp. 613-618 ◽  
Author(s):  
B. F. Robinson ◽  
R. J. W. Phillips
Keyword(s):  
Calcium Concentration ◽  
Venous Blood ◽  
Normal Subjects ◽  
Plasma Calcium ◽  
Calcium Handling ◽  
Membrane Function ◽  
Resistance Vessels ◽  
Initial Control ◽  
Plasma Calcium Concentration ◽  
Small Increments

1. The effect of a small increase in local plasma calcium concentration on the responsiveness of the forearm resistance vessels to verapamil has been examined in normal subjects, by using a plethysmographic method with infusion of calcium and other agents into the brachial artery. 2. Infusion of calcium at a rate which increased the concentration in forearm venous blood by about 0.5 mmol/l caused basal blood flow to fall by 19% and the dilator response to verapamil to fall by 35% (n = 8; P<0.02). 3. When, after 46 min, the infusion of calcium was discontinued, the dilator response to verapamil increased to reach a level 53% higher than the initial control (n = 8; P<0.02). 4. Infusion of calcium had no effect on the dilator response to sodium nitroprusside. 5. Infusion of noradrenaline at a rate which caused a greater reduction in basal flow than that induced by calcium had no effect on the response to verapamil. 6. It is concluded that the dilator response to verapamil, which is thought to reflect activity of the potential operated system for calcium entry, is selectively depressed by a small elevation of plasma calcium concentration, but subsequently becomes elevated. These findings point to an important role for calcium in the regulation of membrane function in the resistance vessels and support the view that altered calcium handling may contribute to the development of primary hypertension.

Intracellular calcium levels in the Plasmodium berghei ookinete

Parasitology ◽  
2008 ◽  
Vol 135 (12) ◽  
pp. 1355-1362 ◽  
Author(s):  
I. SIDÉN-KIAMOS ◽  
C. LOUIS
Keyword(s):  
Intracellular Calcium ◽  
Plasmodium Berghei ◽  
Calcium Concentration ◽  
Insect Cells ◽  
Ionophore A23187 ◽  
Rodent Malaria Parasite ◽  
Calcium Indicators ◽  
Intracellular Ca

SUMMARYOokinetes are the motile and invasive stages of Plasmodium parasites in the mosquito host. Here we explore the role of intracellular Ca2+ in ookinete survival and motility as well as in the formation of oocysts in vitro in the rodent malaria parasite Plasmodium berghei. Treatment with the Ca2+ ionophore A23187 induced death of the parasite, an effect that could be prevented if the ookinetes were co-incubated with insect cells before incubation with the ionophore. Treatment with the intracellular calcium chelator BAPTA/AM resulted in increased formation of oocysts in vitro. Calcium imaging in the ookinete using fluorescent calcium indicators revealed that the purified ookinetes have an intracellular calcium concentration in the range of 100 nm. Intracellular calcium levels decreased substantially when the ookinetes were incubated with insect cells and their motility was concomitantly increased. Our results suggest a pleiotropic role for intracellular calcium in the ookinete.

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