A mathematical model of the vagally driven primary pacemaker

Bristow, DG; Clark, Jr Jw

doi:10.1152/ajpheart.1983.244.1.h150

Cited by 18 publications

(11 citation statements)

References 24 publications

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“…The results presented thus far are qualitatively similar to those recently obtained by Bristow and Clark (1983) in their simulations using a modified version of the McAllister-Noble-Tsien (MNT) model. These authors were also able to reproduce the initial delaying effects of brief vagal trains on pacemaker periodicity.…”

Section: Beating Modesupporting

confidence: 88%

“…This suggests that the equations for the ACh-induced potassium current can reasonably approximate the biological situation. The hyperpolarizations are also similar to those seen by Bristow and Clark (1983) who modeled the vagal stimulus as a brief train of individual ACh pulses. The results can be used to suggest possible ionic mechanisms for the phenomena observed experimentally, and to provide important predictions regarding the dynamic vagal control of heart rate and rhythm.…”

Section: Discussionsupporting

confidence: 75%

“…Consequently, after repolarization, the time-and voltage-dependent increase in inward currents (primarily i s ) became more dominant, thus leading to a slightly less negative (~ 1.5 mV) MDP and to a significant abbreviation of the third cycle. Thus, our results indicate that the secondary acceleration is not dependent on the multicellular nature of the sinus node (Bristow and Clark, 1983), but can be accounted for by the kinetics of the membrane ionic channels alone.…”

Section: Beating Modementioning

confidence: 68%

“…These simulations also show that "paradoxical" acceleration can occur in single-cell pacemakers independent of external factors such as nodal reentry, vagally induced desynchronization, or underlying injury effects (Bristow and Clark, 1983).…”

Section: Influence Of Intrinsic Pacemaker Period On Acetylcholine Effmentioning

confidence: 71%

“…Recently, reports have appeared of attempts to model the cardiac pacemaker by altering the equations from existing nerve and cardiac muscle models (Bristow and Clark, 1982). Bristow and Clark (1983) have investigated the behavior of one of the models of this type when brief vagal pulses are applied. Based on voltage clamp and ion-replacement studies on the sinus node of the rabbit, Yanagihara et al (1980) have reconstructed the action potentials of the sinus pacemaker.…”

mentioning

confidence: 99%

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A mathematical model of the effects of acetylcholine pulses on sinoatrial pacemaker activity.

Michaels¹,

Matyas²,

Jalife³

1984

Circulation Research

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SUMMARY. A mathematical model of dynamic vagus-sinus interactions was devised based on Hodgkin and Huxley-type equations of time-and voltage-dependent membrane currents. Brief vagal pulses were modeled with a concentration-dependent, acetylcholine-activated, potassium current. Single acetylcholine ('vagal") pulses scanning the sinus cycle induced changes in pacemaker rhythm that depended on pulse magnitude, duration, and time of occurrence during the cycle. Phase-response curves summarizing these effects are strikingly similar to experimental results. Notably, appropriately timed acetylcholine pulses could produce an acceleratory response. With repetitive acetylcholine input, the model produced various patterns of synchronization of the sinus pacemaker. There was stable entrainment at harmonic (i.e., 1:1, 2:1, etc.) relations, as well as more complex arrhythmic patterns that depended on the relationship between the acetylcholine cycle length and the sinus pacemaker period. In some cases, shortening of the acetylcholine input cycle length led to "paradoxical" acceleration of the sinus pacemaker. Simulations suggest that many clinically observed sinus rhythm disturbances can be explained by dynamic vagus-sinus interactions, (tire Res 55: 89-101, 1984)

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Section: Beating Modesupporting

confidence: 88%

Section: Discussionsupporting

confidence: 75%

Section: Beating Modementioning

confidence: 68%

Section: Influence Of Intrinsic Pacemaker Period On Acetylcholine Effmentioning

confidence: 71%

mentioning

confidence: 99%

See 3 more Smart Citations

A mathematical model of the effects of acetylcholine pulses on sinoatrial pacemaker activity.

Michaels¹,

Matyas²,

Jalife³

1984

Circulation Research

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Tetrodotoxin-sensitive inactivation-resistant sodium channels in pacemaker cells influence heart rate

Saint

Gage

1996

Pflügers Arch.

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There is currently some uncertainty about whether cardiac pacemaker cells contain tetrodotoxin (TTX)-sensitive Na+ channels although TTX is known to slow heart rate. We have recorded transient and persistent single-channel currents activated by depolarization in myocytes isolated from the toad sinus venosus. The myocytes were identified as pacemaker cells by their characteristic morphology, spontaneous action potentials that were blocked by cobalt but not by TTX, and lack of an inwardly rectifying K+ current. The voltage dependence of the single-channel currents, their presence in solutions containing no K+ or Ca2+, or in solutions to which Cs+ and Co2+ had been added, their dependence on [Na+] and their sensitivity to TTX indicated that they were Na+ channel currents. The persistent Na+ channel currents were resistant to inactivation and were activated over the range of potentials that occur during diastole in pacemaker cells: they would therefore contribute to the pacemaker current that sets heart rate. It was concluded that TTX slows heart rate by blocking these channels in pacemaker cells.

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