Pulmonary vein sleeve cell excitation–contraction-coupling becomes dysynchronized by spontaneous calcium transients

2015 ◽  
Vol 43 (3) ◽  
pp. 410-416 ◽  
Author(s):  
Katja Rietdorf ◽  
Said Masoud ◽  
Fraser McDonald ◽  
Michael J. Sanderson ◽  
Martin D. Bootman
Keyword(s):  
Spontaneous Activity ◽  
Pulmonary Vein ◽  
Action Potentials ◽  
Pulmonary Veins ◽  
Electrical Field Stimulation ◽  
Spontaneous Action ◽  
Major Treatment ◽  
Electrical Pacing ◽  
Electrical Stimuli ◽  
Spontaneous Action Potentials

Atrial fibrillation (AF) is the most common form of sustained cardiac arrhythmia. Substantial evidence indicates that cardiomyocytes located in the pulmonary veins [pulmonary vein sleeve cells (PVCs)] cause AF by generating ectopic electrical activity. Electrical ablation, isolating PVCs from their left atrial junctions, is a major treatment for AF. In small rodents, the sleeve of PVCs extends deep inside the lungs and is present in lung slices. Here we present data, using the lung slice preparation, characterizing how spontaneous Ca2+ transients in PVCs affect their capability to respond to electrical pacing. Immediately after a spontaneous Ca2+ transient the cell is in a refractory period and it cannot respond to electrical stimulation. Consequently, we observe that the higher the level of spontaneous activity in an individual PVC, the less likely it is that this PVC responds to electrical field stimulation. The spontaneous activity of neighbouring PVCs can be different from each other. Heterogeneity in the Ca2+ signalling of cells and in their responsiveness to electrical stimuli are known pro-arrhythmic events. The tendency of PVCs to show spontaneous Ca2+ transients and spontaneous action potentials (APs) underlies their potential to cause AF.

scholarly journals Simulation of spontaneous action potentials of cardiomyocytes in pulmonary veins of rabbits

2008 ◽  
Vol 96 (1-3) ◽  
pp. 132-151 ◽  
Author(s):  
Chang Ahn Seol ◽  
Jun Kim ◽  
Won Tae Kim ◽  
Jeong Mi Ha ◽  
Han Choe ◽  
...  
Keyword(s):  
Action Potentials ◽  
Pulmonary Veins ◽  
Spontaneous Action ◽  
Spontaneous Action Potentials

Inactivation of the calcium current is involved in overdrive suppression of rabbit sinoatrial node cells

1996 ◽  
Vol 271 (5) ◽  
pp. H2097-H2107
Author(s):  
E. I. Watanabe ◽  
H. Honjo ◽  
M. R. Boyett ◽  
I. Kodama ◽  
J. Toyama
Keyword(s):  
Spontaneous Activity ◽  
Voltage Clamp ◽  
High Frequency ◽  
Action Potentials ◽  
Delayed Rectifier ◽  
Patch Clamp Technique ◽  
Sa Node ◽  
Spontaneous Action ◽  
Overdrive Suppression ◽  
Spontaneous Action Potentials

The contribution of inactivation of the L-type Ca2+ current (iCa) to overdrive suppression was investigated in rabbit sinoatrial (SA) node cells by use of the whole cell patch-clamp technique. In the current-clamp mode, rapid stimulation (6.7 Hz) for 30 s was followed by a transient increase in the cycle length of spontaneous action potentials of 135 +/- 52% (n = 3), i.e., "overdrive suppression." The iCa was measured in the voltage-clamp mode in the presence of 30 microM tetrodotoxin. An increase in the rate of depolarizing pulses (to 0 mV for 100 ms) from 1 to 6.7 Hz from a holding potential (HP) of -40 mV resulted in an abrupt, followed by a progressive, decrease in iCa; after 30 s of stimulation at 6.7 Hz, iCa was reduced to 15.5 +/- 1.8% (n = 4) of the control at 1 Hz. With an HP of -80 mV, a similar increase in the pulse rate caused much less reduction in iCa. When spontaneous action potentials were interrupted by a 30-s train of high-frequency voltage-clamp pulses (to 0 mV for 100 ms; 6.7 Hz) from an HP of -40 mV, there was again a marked decrease in iCa during the train, and after the train there was a transient suppression of spontaneous activity. In contrast, a similar interruption by high-frequency voltage-clamp pulses from an HP of -80 mV caused no decrease in iCa, and there was no suppression of spontaneous activity after the train. Neither delayed rectifier K+ current nor hyperpolarization-activated current was affected after a train of high-frequency voltage-clamp pulses. These findings suggest that overdrive suppression in the SA node is, in part at least, the result of a rate- and voltage-dependent inactivation of iCa.

scholarly journals Mechanisms Underlying Spontaneous Action Potential Generation Induced by Catecholamine in Pulmonary Vein Cardiomyocytes: A Simulation Study

2019 ◽  
Vol 20 (12) ◽  
pp. 2913 ◽  
Author(s):  
Shohei Umehara ◽  
Xiaoqiu Tan ◽  
Yosuke Okamoto ◽  
Kyoichi Ono ◽  
Akinori Noma ◽  
...  
Keyword(s):  
Action Potentials ◽  
Ryanodine Receptors ◽  
Pulmonary Veins ◽  
Resting Potential ◽  
Ip3 Receptors ◽  
Spontaneous Action Potential ◽  
Spontaneous Action ◽  
Positive And Negative Feedback ◽  
Time Courses ◽  
Spontaneous Action Potentials

Cardiomyocytes and myocardial sleeves dissociated from pulmonary veins (PVs) potentially generate ectopic automaticity in response to noradrenaline (NA), and thereby trigger atrial fibrillation. We developed a mathematical model of rat PV cardiomyocytes (PVC) based on experimental data that incorporates the microscopic framework of the local control theory of Ca2+ release from the sarcoplasmic reticulum (SR), which can generate rhythmic Ca2+ release (limit cycle revealed by the bifurcation analysis) when total Ca2+ within the cell increased. Ca2+ overload in SR increased resting Ca2+ efflux through the type II inositol 1,4,5-trisphosphate (IP3) receptors (InsP3R) as well as ryanodine receptors (RyRs), which finally triggered massive Ca2+ release through activation of RyRs via local Ca2+ accumulation in the vicinity of RyRs. The new PVC model exhibited a resting potential of −68 mV. Under NA effects, repetitive Ca2+ release from SR triggered spontaneous action potentials (APs) by evoking transient depolarizations (TDs) through Na+/Ca2+ exchanger (APTDs). Marked and variable latencies initiating APTDs could be explained by the time courses of the α1- and β1-adrenergic influence on the regulation of intracellular Ca2+ content and random occurrences of spontaneous TD activating the first APTD. Positive and negative feedback relations were clarified under APTD generation.

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