Downward gradient in action potential duration along conduction path in and around the sinoatrial node

1999 ◽  
Vol 276 (2) ◽  
pp. H686-H698 ◽  
Author(s):  
M. R. Boyett ◽  
H. Honjo ◽  
M. Yamamoto ◽  
M. R. Nikmaram ◽  
R. Niwa ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Sinoatrial Node ◽  
Pacemaker Activity ◽  
Similar Data ◽  
Conduction Path ◽  
Crista Terminalis ◽  
Conduction Pathway ◽  
Pacemaker Shift ◽  
Rabbit Sinoatrial Node

Regional differences in electrical activity in rabbit sinoatrial node have been investigated by recording action potentials throughout the intact node or from small balls of tissue from different regions. In the intact node, action potential duration was greatest at or close to the leading pacemaker and declined markedly in all directions from it, e.g., by 74 ± 4% (mean ± SE, n = 4) to the crista terminalis. Similar data were obtained from the small balls. The gradient is down the conduction pathway and will help prevent reentry. In the intact node, a zone of inexcitable tissue with small depolarizations of <25 mV or stable resting potentials was discovered in the inferior part of the node, and this will again help prevent reentry. The intrinsic pacemaker activity of the small balls was slower in tissue from more inferior (as well as more central) parts of the node [e.g., cycle length increased from 339 ± 13 ms ( n = 6) to 483 ± 13 ms ( n = 6) in transitional tissue from more superior and inferior sites], and this may help explain pacemaker shift.

scholarly journals Isoprenaline: A Potential Contributor in Sick Sinus Syndrome—Insights from a Mathematical Model of the Rabbit Sinoatrial Node

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Xiang Li ◽  
Ji-qian Zhang ◽  
Jian-wei Shuai
Keyword(s):  
Action Potential ◽  
Sinoatrial Node ◽  
Sick Sinus Syndrome ◽  
Surrounding Tissue ◽  
Pacemaker Activity ◽  
Histological Structure ◽  
Cell Models ◽  
Peripheral Cell ◽  
Positive Effects ◽  
Rabbit Sinoatrial Node

The mechanism of isoprenaline exerting its effects on cardiac pacemaking and driving in sick sinus syndrome is controversial and unresolved. In this paper, mathematical models for rabbit sinoatrial node cells were modified by incorporating equations for the known dose-dependent actions of isoprenaline on various ionic channel currents, the intracellular Ca2+transient, andiNachanges induced by SCN5A gene mutations; the cell models were also incorporated into an intact SAN-atrium model of the rabbit heart that is based on both heterogeneities of the SAN electrophysiology and histological structure. Our results show that, in both central and peripheral cell models, isoprenaline could not only shorten the action potential duration, but also increase the amplitude of action potential. The mutation impaired the SAN pacemaking. Simulated vagal nerve activity amplified the bradycardic effects of the mutation. However, in tissue case, the pacemaker activity may show temporal, spatial, or even spatiotemporal cessation caused by the mutation. Addition of isoprenaline could significantly diminish the bradycardic effect of the mutation and the SAN could restart pacing and driving the surrounding tissue. Positive effects of isoprenaline may primarily be attributable to an increase iniNaandiCa,Twhich were reduced by the mutation.

Regional differences in effects of 4-aminopyridine within the sinoatrial node

1998 ◽  
Vol 275 (4) ◽  
pp. H1158-H1168 ◽  
Author(s):  
M. R. Boyett ◽  
H. Honjo ◽  
M. Yamamoto ◽  
M. R. Nikmaram ◽  
R. Niwa ◽  
...  
Keyword(s):  
Action Potential ◽  
Regional Differences ◽  
Sinoatrial Node ◽  
Outward Current ◽  
Peripheral Tissue ◽  
Transient Outward Current ◽  
Pacemaker Activity ◽  
Small Ball ◽  
Tissue Differences ◽  
Rabbit Sinoatrial Node

4-Aminopyridine (4-AP)-sensitive transient outward current ( I to) has been observed in the sinoatrial node, but its role is unknown. The effect of block of I to by 5 mM 4-AP on small ball-like tissue preparations (diameter ∼0.3–0.4 mm) from different regions of the rabbit sinoatrial node has been investigated. 4-AP elevated the plateau, prolonged the action potential, and decreased the maximum diastolic potential. Effects were greater in tissue from the periphery of the node than from the center. In peripheral tissue, 4-AP abolished the action potential notch, if present. 4-AP slowed pacemaker activity of peripheral tissue but accelerated that of central tissue. Differences in the response to 4-AP were also observed between tissue from more superior and inferior regions of the node. In the intact sinoatrial node, 4-AP resulted in a shift of the leading pacemaker site consistent with the regional differences in the response to 4-AP. It is concluded that 4-AP-sensitive outward current plays a major role in action potential repolarization and pacemaker activity in the sinoatrial node and that its role varies regionally.

scholarly journals Postganglionic nerve stimulation induces temporal inhibition of excitability in rabbit sinoatrial node

2006 ◽  
Vol 291 (2) ◽  
pp. H612-H623 ◽  
Author(s):  
Vadim V. Fedorov ◽  
William J. Hucker ◽  
Halina Dobrzynski ◽  
Leonid V. Rosenshtraukh ◽  
Igor R. Efimov
Keyword(s):  
Nerve Stimulation ◽  
Connexin 43 ◽  
Sinoatrial Node ◽  
Conduction Block ◽  
Crista Terminalis ◽  
Cell Excitability ◽  
Transient Loss ◽  
Rabbit Sinoatrial Node ◽  
Postganglionic Nerve ◽  
Temporal Inhibition

Vagal stimulation results in complex changes of pacemaker excitability in the sinoatrial node (SAN). To investigate the vagal effects in the rabbit SAN, we used optical mapping, which is the only technology that allows resolving simultaneous changes in the activation pattern and action potentials morphologies. With the use of immunolabeling, we identified the SAN as a neurofilament 160-positive but connexin 43-negative region ( n = 5). Normal excitation originated in the SAN center with a cycle length (CL) of 405 ± 14 ms ( n = 14), spread anisotropically along the crista terminalis (CT), and failed to conduct toward the septum. Postganglionic nerve stimulation (PNS, 400–800 ms) reduced CL by 74 ± 7% transiently and shifted the leading pacemaker inferiorly (78%) or superiorly (22%) from the SAN center by 2–10 mm. In the intercaval region between the SAN center and the septal block zone, PNS produced an 8 ± 1-mm2 region of transient hyperpolarization and inexcitability. The first spontaneous or paced excitation following PNS could not enter this region for 500–1,500 ms. Immunolabeling revealed that the PNS-induced inexcitable region is located between the SAN center and the block zone and has a 2.5-fold higher density of choline acetyltransferase than CT but is threefold lower than the SAN center. The fact that the inexcitability region does not coincide with the most innervated area indicates that the properties of the myocytes themselves, as well as intercellular coupling, must play a role in the inexcitability induction. Optically mapping revealed that PNS resulted in transient loss of pacemaker cell excitability and unidirectional entrance conduction block in the periphery of SAN.

Investigation of pacemaker shift in the rabbit sinoatrial node using the optical mapping technique

BIOPHYSICS ◽  
2010 ◽  
Vol 55 (3) ◽  
pp. 442-446
Author(s):  
D. V. Abramochkin ◽  
V. S. Kuzmin ◽  
G. S. Sukhova ◽  
L. V. Rosenshtraukh
Keyword(s):  
Sinoatrial Node ◽  
Optical Mapping ◽  
Mapping Technique ◽  
Pacemaker Shift ◽  
Rabbit Sinoatrial Node

Regional differences in effects of E-4031 within the sinoatrial node

1999 ◽  
Vol 276 (3) ◽  
pp. H793-H802 ◽  
Author(s):  
I. Kodama ◽  
M. R. Boyett ◽  
M. R. Nikmaram ◽  
M. Yamamoto ◽  
H. Honjo ◽  
...  
Keyword(s):  
Action Potential ◽  
Electrical Activity ◽  
Spontaneous Activity ◽  
Regional Differences ◽  
Sinoatrial Node ◽  
Peripheral Tissue ◽  
Delayed Rectifier ◽  
Small Ball ◽  
Rabbit Sinoatrial Node ◽  
Diastolic Potential

Effects of block of the rapid delayed rectifier K+current ( I K,r) by E-4031 on the electrical activity of small ball-like tissue preparations from different regions of the rabbit sinoatrial node were measured. The effects of partial block of I K,r by 0.1 μM E-4031 varied in different regions of the node. In tissue from the center of the node spontaneous activity was generally abolished, whereas in tissue from the periphery spontaneous activity persisted, although the action potential was prolonged, the maximum diastolic potential was decreased, and the spontaneous activity slowed. After partial block of I K,r, the electrical activity of peripheral tissue was more like that of central tissue under normal conditions. One possible explanation of these findings is that the density of I K,r is greater in the periphery of the node; this would explain the greater resistance of peripheral tissue to I K,r block and help explain why, under normal conditions, the maximum diastolic potential is more negative, the action potential is shorter, and pacemaking is faster in the periphery.

Parasympathetic modulation of sinoatrial node pacemaker activity in rabbit heart: a unifying model

1999 ◽  
Vol 276 (6) ◽  
pp. H2221-H2244 ◽  
Author(s):  
Semahat S. Demir ◽  
John W. Clark ◽  
Wayne R. Giles
Keyword(s):  
Sinoatrial Node ◽  
Vagal Stimulation ◽  
Full Range ◽  
Rabbit Heart ◽  
Pacemaker Activity ◽  
Membrane Hyperpolarization ◽  
Different Types ◽  
Cardiac Pacemaking ◽  
Rabbit Sinoatrial Node ◽  
Diastolic Potential

We have extended our compartmental model [ Am. J. Physiol. 266 ( Cell Physiol. 35): C832–C852, 1994] of the single rabbit sinoatrial node (SAN) cell so that it can simulate cellular responses to bath applications of ACh and isoprenaline as well as the effects of neuronally released ACh. The model employs three different types of muscarinic receptors to explain the variety of responses observed in mammalian cardiac pacemaking cells subjected to vagal stimulation. The response of greatest interest is the ACh-sensitive change in cycle length that is not accompanied by a change in action potential duration or repolarization or hyperpolarization of the maximum diastolic potential. In this case, an ACh-sensitive K+ current is not involved. Membrane hyperpolarization occurs in response to much higher levels of vagal stimulation, and this response is also mimicked by the model. Here, an ACh-sensitive K+ current is involved. The well-known phase-resetting response of the SAN cell to single and periodically applied vagal bursts of impulses is also simulated in the presence and absence of the β-agonist isoprenaline. Finally, the responses of the SAN cell to longer continuous trains of periodic vagal stimulation are simulated, and this can result in the complete cessation of pacemaking. Therefore, this model is 1) applicable over the full range of intensity and pattern of vagal input and 2) can offer biophysically based explanations for many of the phenomena associated with the autonomic control of cardiac pacemaking.

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