Computational Model of Rabbit SA Node Pacemaker Activity Probed with Action Potential and Calcium Transient Clamp

2007 ◽  
Author(s):  
Marcel M. G. J. van Borren ◽  
Jan G. Zegers ◽  
Arie O. Verkerk ◽  
Ronald Wilders
Keyword(s):  
Action Potential ◽  
Computational Model ◽  
Calcium Transient ◽  
Pacemaker Activity ◽  
Sa Node

Effect of hydrogen peroxide on the membrane currents of sinoatrial node cells from rabbit heart

2000 ◽  
Vol 279 (3) ◽  
pp. H992-H999 ◽  
Author(s):  
Jiqing Guo ◽  
Wayne R. Giles ◽  
Christopher A. Ward
Keyword(s):  
Action Potential ◽  
Rabbit Heart ◽  
Membrane Currents ◽  
Delayed Rectifier ◽  
Pacemaker Activity ◽  
Sa Node ◽  
Kinase C ◽  
Short Term Exposure ◽  
Spontaneous Action ◽  
Prolongation Of Action Potential

The effects of H2O2 on pacemaker activity and underlying membrane currents were studied in isolated rabbit sinoatrial (SA) node cells using perforated patch current- and voltage-clamp methods. Short-term exposure (<10 min) of the nodal cells to H2O2 (200 μM) resulted in an initial shortening of spontaneous action potential cycle length (from 445 ± 60 to 398 ± 56 ms; P < 0.05) and a prolongation of action potential duration. H2O2(100 μM) significantly increased peak L-type Ca2+ current ( I Ca,L) from −384 ± 77 to −439 ± 84 pA (116 ± 2%, n = 6). Additionally, the persistent or non-inactivating component of I Ca,L was increased from −52 ± 3 to −88 ± 14 pA (174 ± 19%, n = 6). The hyperpolarization-activated current ( I f) was decreased from −228 ± 62 to −161 ± 72 pA after exposure to H2O2 ( n = 7). There were no changes in the delayed rectifier K+ current ( I K) ( n = 7). H2O2-induced Ca2+ currents were blocked by 2 μM nicardipine ( n = 6), 2 mM Ni2+ ( n = 2), and the protein kinase C (PKC) inhibitor bisindolylmaleimide (10−7 M; n = 4) but not by 20 μM tetrodotoxin. These results suggest that H2O2 can increase the spontaneous pacing rate in rabbit SA node cells by enhancing I Ca,L and that this effect is mediated by a PKC-dependent pathway.

scholarly journals The effect of temperature on spontaneous action potential discharge of the isolated sinus venosus from winter and summer plaice (Pleuronectes platessa)

1995 ◽  
Vol 198 (1) ◽  
pp. 137-140 ◽  
Author(s):  
A A Harper ◽  
I P Newton ◽  
P W Watt
Keyword(s):  
Action Potential ◽  
Discharge Rate ◽  
Cardiac Pacemaker ◽  
Intrinsic Rate ◽  
Effect Of Temperature ◽  
Pacemaker Activity ◽  
Duration Of Action ◽  
Diastolic Depolarization ◽  
Significant Difference

The spontaneous cardiac pacemaker activity and conformation were recorded in vitro, using intracellular recording methods, from heart tissue of summer- and winter-caught plaice. The effects of changing temperature on the pacemaker rate, duration of action potential and diastolic depolarization were investigated by altering the temperature of the superfusing medium. The resting intrinsic rate of discharge was significantly greater in pacemaker cells from winter plaice (P=0.05), but there was no significant difference between winter and summer fish in the apparent Arrhenius activation energies for this process. However, there was a significant difference in the estimated intercept, indicating a thermal shift in the processes underlying the spontaneous pacemaker rhythm. There was no significant difference in the diastolic depolarization duration recorded from winter and summer fish over the temperature range 4&shy;22 &deg;C. The major effect of previous environmental temperature was on the duration of the action potential (P&lt;0.02), indicating that the observed changes in pacemaker discharge rate were not influenced by the processes that determine the duration of the pacemaker diastolic depolarisation but were modulated by the channel events that give rise to the action potential.

scholarly journals Effects of Serum Calcium Changes on the Cardiac Action Potential and the ECG in a Computational Model

2018 ◽  
Vol 4 (1) ◽  
pp. 251-254 ◽  
Author(s):  
María Hernández Mesa ◽  
Nicolas Pilia ◽  
Olaf Dössel ◽  
Stefano Severi ◽  
Axel Loewe
Keyword(s):  
Action Potential ◽  
Computational Model ◽  
Cell Model ◽  
Cellular Level ◽  
Calcium Dependent ◽  
Cardiac Action ◽  
Dependent Inactivation ◽  
End Stage ◽  
Extracellular Sodium ◽  
Ventricular Cell Model

AbstractPatients suffering from end stage of chronic kidney disease (CKD) often undergo haemodialysis to normalize the electrolyte concentrations. Moreover, cardiovascular disease (CVD) is the main cause of death in CKD patients. To study the connection between CKD and CVD, we investigated the effects of an electrolyte variation on cardiac signals (action potential and ECG) using a computational model. In a first step, simulations with the Himeno et al. ventricular cell model were performed on cellular level with different extracellular sodium ([Na+]o), calcium ([Ca2+]o) and potassium ([K+]o) concentrations as occurs in CKD patients. [Ca2+]o and [K+]o changes caused variations in different features describing the morphology of the AP. Changes due to a [Na+]o variation were not as prominent. Simulations with [Ca2+]o variations were also carried out on ventricular ECG level and a 12-lead ECG was computed. Thus, a multiscale simulator from ion channel to ECG reproducing the calcium-dependent inactivation of ICaL was achieved. The results on cellular and ventricular level agree with results from literature. Moreover, we suggest novel features representing electrolyte changes that have not been described in literature. These results could be helpful for further studies aiming at the estimation of ionic concentrations based on ECG recordings.

scholarly journals PHARMACOLOGIC ANALYSIS OF NICOTINE AND DIMETHYLPHENYLPIPERAZINIUM ON PACEMAKER ACTIVITY OF THE SA NODE IN THE DOG

1972 ◽  
Vol 22 (5) ◽  
pp. 645-651 ◽  
Author(s):  
Shigetoshi CHIBA ◽  
Kiyoshi TAMURA ◽  
Katsumi KUBOTA ◽  
Koroku HASHIMOTO
Keyword(s):  
Pacemaker Activity ◽  
Sa Node ◽  
Pharmacologic Analysis

Effect of Several Cations on Transmembrane Potentials of Cardiac Muscle

1956 ◽  
Vol 186 (2) ◽  
pp. 317-324 ◽  
Author(s):  
Brian F. Hoffman ◽  
E. E. Suckling
Keyword(s):  
Action Potential ◽  
Cardiac Muscle ◽  
Action Potentials ◽  
Time Course ◽  
Pacemaker Activity ◽  
Transmembrane Potentials ◽  
High K ◽  
Intracellular Microelectrodes ◽  
Simultaneous Decrease ◽  
Low K

The effects of changes in the extracellular concentrations of Ca, K and Mg on the transmembrane resting and action potentials of single fibers of the auricle, ventricle and specialized conducting system of the dog heart have been studied by means of intracellular microelectrodes. With respect to Ca, the three tissues exhibit quite different sensitivities. Changes in concentration of this ion alter the time course of the action potential recorded from auricle and ventricle but have little effect on the action potential configuration of the Purkinje fiber. In the latter tissue, on the other hand, pacemaker activity is most strongly enhanced by Ca depletion and excitability is lost at Ca concentrations permitting normal propagation in papillary muscle. The effect of K on the resting transmembrane potential is dependent on the simultaneous Ca concentration. The interrelationship is such that the depolarizing effect of high K is decreased by elevated Ca and the depolarization produced by low K is diminished by low levels of Ca. Changes in the concentration of Mg have little effect on the transmembrane potentials of cardiac muscle unless the level of Ca is low. Under this condition a simultaneous decrease in Mg gives rise to a marked prolongation of the action potential duration of both auricle and ventricle. Some evidence for the basic similarity of the processes underlying repolarization in these three tissues is presented and it is thought the normally encountered differences in their action potentials may be related to the sensitivity of each tissue to extracellular Ca.

Presynaptic Ca2+ Influx at the Inhibitor of the Crayfish Neuromuscular Junction: A Photometric Study at a High Time Resolution

2000 ◽  
Vol 83 (1) ◽  
pp. 552-562 ◽  
Author(s):  
Andrey Vyshedskiy ◽  
Jen-Wei Lin
Keyword(s):  
Action Potential ◽  
Time Resolution ◽  
Transmitter Release ◽  
Calcium Influx ◽  
Calcium Transient ◽  
High Time ◽  
High Time Resolution ◽  
Presynaptic Calcium ◽  
Crayfish Neuromuscular Junction ◽  
Fluorescence Transients

Presynaptic calcium influx at the inhibitor of the crayfish neuromuscular junction was investigated by measuring fluorescence transients generated by calcium-sensitive dyes. This approach allowed us to correlate presynaptic calcium influx with transmitter release at a high time resolution. Systematic testing of the calcium indicators showed that only low-affinity dyes, with affinities in the range of micromolar, should be used to avoid saturation of dye binding and interference with transmitter release. Presynaptic calcium influx was regulated by slowly increasing the duration of the action potential through progressive block of potassium channels. The amplitude of the calcium transient, measured from a cluster of varicosities, was linearly related to the duration of the action potential with a slope of 1.2. Gradual changes in potassium channel block allowed us to estimate the calcium cooperativity of transmitter release over a 10-fold range in presynaptic calcium influx. Calcium cooperativity measured here exhibited one component with an average value of 3.1. Inspection of simultaneously recorded presynaptic calcium transients and inhibitory postsynaptic currents (IPSCs) showed that prolonged action potentials were associated with a slow rising phase of presynaptic calcium transients, which were matched by a slow rate of rise of IPSCs. The close correlation suggests that fluorescence transients provide information on the rate of calcium influx. Because there is an anatomic mismatch between the presynaptic calcium transient, measured from a cluster of varicosities, and IPSC, measured with two-electrode voltage clamp, macropatch recording was used to monitor inhibitory postsynaptic responses from the same cluster of varicosities from which the calcium transient was measured. Inhibitory postsynaptic responses recorded with the macropatch method exhibited a faster rising phase than that recorded with two-electrode voltage clamp. This difference could be attributed to slight asynchrony of transmitter release due to action potential conduction along fine branches. In conclusion, this report shows that fluorescence transients generated by calcium-sensitive dyes can provide insights to the properties of presynaptic calcium influx, and its correlation with transmitter release, at a high time resolution.

Electrotonic interactions in delayed propagation and block within the guinea pig SA node

1983 ◽  
Vol 245 (1) ◽  
pp. H7-H16 ◽  
Author(s):  
S. L. Lipsius
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Action Potential Duration ◽  
Progressive Increase ◽  
Pacemaker Cells ◽  
Sa Node ◽  
Transmembrane Potentials ◽  
Electrotonic Interactions ◽  
Rapid Pacing ◽  
Exit Block

The influence of electrotonic interactions on propagation within the SA node was studied by recording transmembrane potentials simultaneously from two neighboring (less than 1 mm apart) subsidiary pacemaker cells within the sinoatrial (SA) node of the guinea pig. As single premature stimuli were delivered progressively earlier in diastole, retrograde propagation between cells was delayed progressively. Cells activated earlier displayed secondary depolarizations that were coincident with the depolarization of neighboring cells activated later. The secondary depolarizations increased action potential duration markedly. Rapid pacing elicited secondary depolarizations that resulted in a progressive increase in action potential duration and decrease in upstroke amplitude. These changes were associated with a progressive delay in retrograde propagation that led to intermittent block with Wenckebach periodicity. Exposure to tetrodotoxin (10(-5) g/ml) delayed antegrade propagation, resulting in electrotonically mediated secondary depolarizations and exit block with Wenckebach periodicity. It is concluded that delayed activation and electrotonically mediated interactions between cells can increase action potential duration and refractoriness. These changes contribute to progressive delays in propagation that may result in intermittent block with Wenckebach periodicity within the SA node.

scholarly journals A computational model for how the fast afterhyperpolarization paradoxically increases gain in regularly firing neurons

2018 ◽  
Vol 119 (4) ◽  
pp. 1506-1520 ◽  
Author(s):  
David B. Jaffe ◽  
Robert Brenner
Keyword(s):  
Action Potential ◽  
Computational Model ◽  
Interspike Interval ◽  
Computational Study ◽  
Stimulus Frequency ◽  
Bk Channels ◽  
Neuronal Firing ◽  
Inward Current ◽  
Action Potential Waveform ◽  
Potential Waveform

The gain of a neuron, the number and frequency of action potentials triggered in response to a given amount of depolarizing injection, is an important behavior underlying a neuron’s function. Variations in action potential waveform can influence neuronal discharges by the differential activation of voltage- and ion-gated channels long after the end of a spike. One component of the action potential waveform, the afterhyperpolarization (AHP), is generally considered an inhibitory mechanism for limiting firing rates. In dentate gyrus granule cells (DGCs) expressing fast-gated BK channels, large fast AHPs (fAHP) are paradoxically associated with increased gain. In this article, we describe a mechanism for this behavior using a computational model. Hyperpolarization provided by the fAHP enhances activation of a dendritic inward current (a T-type Ca2+ channel is suggested) that, in turn, boosts rebound depolarization at the soma. The model suggests that the fAHP may both reduce Ca2+ channel inactivation and, counterintuitively, enhance its activation. The magnitude of the rebound depolarization, in turn, determines the activation of a subsequent, slower inward current (a persistent Na+ current is suggested) limiting the interspike interval. Simulations also show that the effect of AHP on gain is also effective for physiologically relevant stimulation; varying AHP amplitude affects interspike interval across a range of “noisy” stimulus frequency and amplitudes. The mechanism proposed suggests that small fAHPs in DGCs may contribute to their limited excitability. NEW & NOTEWORTHY The afterhyperpolarization (AHP) is canonically viewed as a major factor underlying the refractory period, serving to limit neuronal firing rate. We recently reported that enhancing the amplitude of the fast AHP (fAHP) in a relatively slowly firing neuron (vs. fast spiking neurons) expressing fast-gated BK channels augments neuronal excitability. In this computational study, we present a novel, quantitative hypothesis for how varying the amplitude of the fAHP can, paradoxically, influence a subsequent spike tens of milliseconds later.

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