Alendronate has an arrhythmogenic effect on cardiomyocytes in vitro by affecting calcium dynamics

Bone ◽  
2009 ◽  
Vol 44 ◽  
pp. S75
Author(s):  
N. Kemeny-Suss ◽  
A. Kasneci ◽  
D. Rivas ◽  
J. Afilalo ◽  
L. Chalifour ◽  
...  
Keyword(s):  
Calcium Dynamics ◽  
Arrhythmogenic Effect

Intracellular calcium dynamics and cerebral injury: modeling various insults in vitro

1993 ◽  
Vol 613 (1) ◽  
pp. 156-159 ◽  
Author(s):  
Myung H. Kim-Lee ◽  
Bradford T. Stokes ◽  
Douglas K. Anderson
Keyword(s):  
Intracellular Calcium ◽  
Cerebral Injury ◽  
Calcium Dynamics ◽  
Intracellular Calcium Dynamics

Activity-Related Calcium Dynamics in Motoneurons of the Nucleus Hypoglossus From Mouse

1999 ◽  
Vol 82 (6) ◽  
pp. 2936-2946 ◽  
Author(s):  
Mario B. Lips ◽  
Bernhard U. Keller
Keyword(s):  
Quantitative Analysis ◽  
Action Potential ◽  
Calcium Binding ◽  
Calcium Influx ◽  
Binding Capacity ◽  
Calcium Transients ◽  
Calcium Dynamics ◽  
The Brain

A quantitative analysis of activity-related calcium dynamics was performed in motoneurons of the nucleus hypoglossus in the brain stem slice preparation from mouse by simultaneous patch-clamp and microfluorometric calcium measurements. Motoneurons were analyzed under in vitro conditions that kept them in a functionally intact state represented by rhythmic, inspiratory-related bursts of excitatory postsynaptic currents and associated action potential discharges. Bursts of electrical activity were paralleled by somatic calcium transients resulting from calcium influx through voltage-activated calcium channels, where each action potential accounted for a calcium-mediated charge influx around 2 pC into the somatic compartment. Under in vivo conditions, rhythmic-respiratory activity in young mice occurred at frequencies up to 5 Hz, demonstrating the necessity for rapid calcium elevation and recovery in respiratory-related neurons. The quantitative analysis of hypoglossal calcium homeostasis identified an average extrusion rate, but an exceptionally low endogenous calcium binding capacity as cellular parameters accounting for rapid calcium signaling. Our results suggest that dynamics of somatic calcium transients 1) define an upper limit for the maximum frequency of respiratory-related burst discharges and 2) represent a potentially dangerous determinant of intracellular calcium profiles during pathophysiological and/or excitotoxic conditions.

scholarly journals Intracellular calcium dynamics at the core of endocardial stationary spiral waves in Langendorff-perfused rabbit hearts

2008 ◽  
Vol 295 (1) ◽  
pp. H297-H304 ◽  
Author(s):  
Liang Tang ◽  
Gyo-Seung Hwang ◽  
Hideki Hayashi ◽  
Juan Song ◽  
Masahiro Ogawa ◽  
...  
Keyword(s):  
Intracellular Calcium ◽  
Transmembrane Potential ◽  
Spiral Wave ◽  
In Vitro Models ◽  
Spiral Waves ◽  
Calcium Dynamics ◽  
The Core ◽  
Intracellular Calcium Dynamics ◽  
The Right

In vitro models of sustained monomorphic ventricular tachycardia (MVT) are rare and do not usually show spiral reentry on the epicardium. We hypothesized that MVT is associated with the spiral wave in the endocardium and that this stable reentrant propagation is supported by a persistently elevated intracellular calcium (Cai) transient at the core of the spiral wave. We performed dual optical mapping of transmembrane potential ( Vm) and Cai dynamics of the right ventricular (RV) endocardium in Langendorff-perfused rabbit hearts ( n = 12). Among 64 induced arrhythmias, 55% were sustained MVT (>10 min). Eighty percent of MVT showed stationary spiral waves (>10 cycles, cycle length: 128 ± 14.6 ms) in the endocardial mapped region, anchoring to the anatomic discontinuities. No reentry activity was observed in the epicardium. During reentry, the amplitudes of Vm and Cai signals were higher in the periphery and gradually decreased toward the core. At the core, maximal Vm and Cai amplitudes were 42.95 ± 5.89% and 43.95 ± 9.46%, respectively, of the control ( P < 0.001). However, the trough of the Vm and Cai signals at the core were higher than those in the periphery, indicating persistent Vm and Cai elevations during reentry. BAPTA-AM, a calcium chelator, significantly reduced the maximal Cai transient amplitude and prevented sustained MVT and spiral wave formation in the mapped region. These findings indicate that endocardial spiral waves often anchor to anatomic discontinuities causing stable MVT in normal rabbit ventricles. The spiral core is characterized by diminished Vm and Cai amplitudes and persistent Vm and Cai elevations during reentry.

Manipulating Senescence of Cardiac Fibroblasts In Vivo and In Vitro to Investigate Arrhythmogenic Effect of Senescence

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Elif Sengun ◽  
Brett Baggett ◽  
Kevin Murphy ◽  
Yichun Lu ◽  
Tae-Yun Kim ◽  
...  
Keyword(s):  
Cardiac Fibroblasts ◽  
Arrhythmogenic Effect

In vivo or in vitro imaging of calcium dynamics with genetically encoded sensor G-CaMP4

2010 ◽  
Vol 68 ◽  
pp. e443
Author(s):  
Atsushi Usami ◽  
Keiko Ando ◽  
Masamichi Ohkura ◽  
Norio Matsuki ◽  
Yuji Ikegaya ◽  
...  
Keyword(s):  
Calcium Dynamics

scholarly journals Design and mechanistic insight into ultrafast calcium indicators for monitoring intracellular calcium dynamics

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Nordine Helassa ◽  
Borbala Podor ◽  
Alan Fine ◽  
Katalin Török
Keyword(s):  
Intracellular Calcium ◽  
Action Potentials ◽  
Rational Design ◽  
Calcium Transients ◽  
Calcium Dynamics ◽  
Binding Interface ◽  
Calcium Indicators ◽  
Slow Kinetics ◽  
Decay Times

Abstract Calmodulin-based genetically encoded fluorescent calcium indicators (GCaMP-s) are powerful tools of imaging calcium dynamics from cells to freely moving animals. High affinity indicators with slow kinetics however distort the temporal profile of calcium transients. Here we report the development of reduced affinity ultrafast variants of GCaMP6s and GCaMP6f. We hypothesized that GCaMP-s have a common kinetic mechanism with a rate-limiting process in the interaction of the RS20 peptide and calcium-calmodulin. Therefore we targeted specific residues in the binding interface by rational design generating improved indicators with GCaMP6f u displaying fluorescence rise and decay times (t 1/2) of 1 and 3 ms (37 °C) in vitro, 9 and 22-fold faster than GCaMP6f respectively. In HEK293T cells, GCaMP6f u revealed a 4-fold faster decay of ATP-evoked intracellular calcium transients than GCaMP6f. Stimulation of hippocampal CA1 pyramidal neurons with five action potentials fired at 100 Hz resulted in a single dendritic calcium transient with a 2-fold faster rise and 7-fold faster decay time (t 1/2 of 40 ms) than GCaMP6f, indicating that tracking high frequency action potentials may be limited by calcium dynamics. We propose that the design strategy used for generating GCaMP6f u is applicable for the acceleration of the response kinetics of GCaMP-type calcium indicators.

scholarly journals Inducible cardiac arrhythmias caused by enhanced β1-adrenergic autoantibody expression in the rabbit

2014 ◽  
Vol 306 (3) ◽  
pp. H422-H428 ◽  
Author(s):  
Hongliang Li ◽  
Benjamin J. Scherlag ◽  
David C. Kem ◽  
Alexandria Benbrook ◽  
Xiaohua Shen ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Sinus Tachycardia ◽  
Specific Binding ◽  
Electrophysiological Study ◽  
Cross Reactivity ◽  
Independent Effect ◽  
Arrhythmogenic Effect ◽  
Before And After ◽  
Activating Autoantibodies

Previous studies demonstrated burst pacing and intravenous infusion of ACh induced sustained atrial tachycardia when rabbits were immunized to produce β2-adrenergic receptor (β2AR)-activating autoantibodies. The objective of this study was to examine the arrhythmogenic effect of β1-adrenergic receptor (β1AR)-activating autoantibodies in the rabbit. Eight New Zealand white rabbits were immunized with a β1AR second extracellular loop peptide to raise β1AR antibody titers. A catheter-based electrophysiological study was performed on anesthetized rabbits before and after immunization. Arrhythmia occurrence was determined in response to burst pacing before and after ACh infusion in incremental concentrations of 10 μM, 100 μM, and 1 mM. The baseline sinus heart rate before and after immunization averaged 149 ± 17 per min and 169 ± 16 per min, respectively ( P < 0.05). In the preimmune studies, there were five sustained (≥10 s) arrhythmias in 32 induction attempts, which occurred in only four of eight rabbits. In the postimmune studies, there were 22 sustained arrhythmias in 32 induction attempts, which occurred in all eight rabbits ( P < 0.0001 for the independent effect of immunization). Of the 22 sustained arrhythmias postimmunization, 15 were sinus tachycardia compared with only two before immunization ( P < 0.01 for the independent effect of immunization). Postimmune (but not preimmune) rabbit sera demonstrated specific binding to β1AR and induced significant β1AR activation in transfected cells in vitro. No cross-reactivity with β2AR was observed. In conclusion, in contrast with rabbits with β2AR-activating autoantibodies that demonstrate predominantly atrial tachycardias, enhanced autoantibody activation of β1AR in the rabbit leads to tachyarrhythmias mainly in the form of sustained sinus tachycardia.

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