scholarly journals Ionic Mechanisms Underlying the Positive Chronotropy Induced by β1-Adrenergic Stimulation in Guinea Pig Sinoatrial Node Cells: a Simulation Study

2008 ◽  
Vol 58 (1) ◽  
pp. 53-65 ◽  
Author(s):  
Yukiko Himeno ◽  
Nobuaki Sarai ◽  
Satoshi Matsuoka ◽  
Akinori Noma
Keyword(s):  
Guinea Pig ◽  
Simulation Study ◽  
Sinoatrial Node ◽  
Adrenergic Stimulation ◽  
Ionic Mechanisms ◽  
Sinoatrial Node Cells

scholarly journals Hierarchical clustering of ryanodine receptors enables emergence of a calcium clock in sinoatrial node cells

2014 ◽  
Vol 143 (5) ◽  
pp. 577-604 ◽  
Author(s):  
Michael D. Stern ◽  
Larissa A. Maltseva ◽  
Magdalena Juhaszova ◽  
Steven J. Sollott ◽  
Edward G. Lakatta ◽  
...  
Keyword(s):  
Hierarchical Clustering ◽  
Calcium Release ◽  
Sinoatrial Node ◽  
Sinus Node ◽  
Ryanodine Receptors ◽  
Membrane Currents ◽  
Immunofluorescent Staining ◽  
Adrenergic Stimulation ◽  
Beating Rate ◽  
Sinoatrial Node Cells

The sinoatrial node, whose cells (sinoatrial node cells [SANCs]) generate rhythmic action potentials, is the primary pacemaker of the heart. During diastole, calcium released from the sarcoplasmic reticulum (SR) via ryanodine receptors (RyRs) interacts with membrane currents to control the rate of the heartbeat. This “calcium clock” takes the form of stochastic, partially periodic, localized calcium release (LCR) events that propagate, wave-like, for limited distances. The detailed mechanisms controlling the calcium clock are not understood. We constructed a computational model of SANCs, including three-dimensional diffusion and buffering of calcium in the cytosol and SR; explicit, stochastic gating of individual RyRs and L-type calcium channels; and a full complement of voltage- and calcium-dependent membrane currents. We did not include an anatomical submembrane space or inactivation of RyRs, the two heuristic components that have been used in prior models but are not observed experimentally. When RyRs were distributed in discrete clusters separated by >1 µm, only isolated sparks were produced in this model and LCR events did not form. However, immunofluorescent staining of SANCs for RyR revealed the presence of bridging RyR groups between large clusters, forming an irregular network. Incorporation of this architecture into the model led to the generation of propagating LCR events. Partial periodicity emerged from the interaction of LCR events, as observed experimentally. This calcium clock becomes entrained with membrane currents to accelerate the beating rate, which therefore was controlled by the activity of the SERCA pump, RyR sensitivity, and L-type current amplitude, all of which are targets of β-adrenergic–mediated phosphorylation. Unexpectedly, simulations revealed the existence of a pathological mode at high RyR sensitivity to calcium, in which the calcium clock loses synchronization with the membrane, resulting in a paradoxical decrease in beating rate in response to β-adrenergic stimulation. The model indicates that the hierarchical clustering of surface RyRs in SANCs may be a crucial adaptive mechanism. Pathological desynchronization of the clocks may explain sinus node dysfunction in heart failure and RyR mutations.

Particular Sensitivity of the Mammalian Heart Sinus Node Cells

Physiology ◽  
1994 ◽  
Vol 9 (2) ◽  
pp. 77-79 ◽  
Author(s):  
J Petit-Jacques ◽  
J Bescond ◽  
P Bois ◽  
J Lenfant
Keyword(s):  
Adenylate Cyclase ◽  
Spontaneous Activity ◽  
Sinoatrial Node ◽  
Sinus Node ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Adrenergic Stimulation ◽  
Mammalian Heart ◽  
Ionic Mechanisms ◽  
Distinctive Property

High resting adenylate cyclase activity, implying a high basal adenosine 3', 5'-cyclic monophosphate level, seems to be a distinctive property of sinoatrial node cells of mammalian heart. This may explain why acetylcholine depresses two ionic mechanisms involved in spontaneous activity of nodal myocytes, via inhibition of adenylate cyclase activity, without previous b-adrenergic stimulation.

Minor contribution of cytosolic Ca2+ transients to the pacemaker rhythm in guinea pig sinoatrial node cells

2011 ◽  
Vol 300 (1) ◽  
pp. H251-H261 ◽  
Author(s):  
Yukiko Himeno ◽  
Futoshi Toyoda ◽  
Hiroyasu Satoh ◽  
Akira Amano ◽  
Chae Young Cha ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Spontaneous Activity ◽  
Sinoatrial Node ◽  
Pacemaker Activity ◽  
Pipette Solution ◽  
Calmodulin Kinase ◽  
Intracellular Ca ◽  
Spontaneous Action ◽  
Sinoatrial Node Cells ◽  
High Doses

The question of the extent to which cytosolic Ca2+ affects sinoatrial node pacemaker activity has been discussed for decades. We examined this issue by analyzing two mathematical pacemaker models, based on the “Ca2+ clock” (C) and “membrane clock” (M) hypotheses, together with patch-clamp experiments in isolated guinea pig sinoatrial node cells. By applying lead potential analysis to the models, the C mechanism, which is dependent on potentiation of Na+/Ca2+ exchange current via spontaneous Ca2+ release from the sarcoplasmic reticulum (SR) during diastole, was found to overlap M mechanisms in the C model. Rapid suppression of pacemaker rhythm was observed in the C model by chelating intracellular Ca2+, whereas the M model was unaffected. Experimental rupturing of the perforated-patch membrane to allow rapid equilibration of the cytosol with 10 mM BAPTA pipette solution, however, failed to decrease the rate of spontaneous action potential within ∼30 s, whereas contraction ceased within ∼3 s. The spontaneous rhythm also remained intact within a few minutes when SR Ca2+ dynamics were acutely disrupted using high doses of SR blockers. These experimental results suggested that rapid disruption of normal Ca2+ dynamics would not markedly affect spontaneous activity. Experimental prolongation of the action potentials, as well as slowing of the Ca2+-mediated inactivation of the L-type Ca2+ currents induced by BAPTA, were well explained by assuming Ca2+ chelation, even in the proximity of the channel pore in addition to the bulk cytosol in the M model. Taken together, the experimental and model findings strongly suggest that the C mechanism explicitly described by the C model can hardly be applied to guinea pig sinoatrial node cells. The possible involvement of L-type Ca2+ current rundown induced secondarily through inhibition of Ca2+/calmodulin kinase II and/or Ca2+-stimulated adenylyl cyclase was discussed as underlying the disruption of spontaneous activity after prolonged intracellular Ca2+ concentration reduction for >5 min.

scholarly journals Electrophysiological effects of endothelins on isolated sinoatrial node cells of rabbit and guinea pig

1997 ◽  
Vol 73 ◽  
pp. 191
Author(s):  
Kageyoshi Ono ◽  
Hikaru Tanaka ◽  
Haruko Masumiya ◽  
Toshinori Shijuku ◽  
Aiji Sakamoto ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Sinoatrial Node ◽  
Sinoatrial Node Cells ◽  
Electrophysiological Effects

scholarly journals Inhibitory effects of sevoflurane on pacemaking activity of sinoatrial node cells in guinea-pig heart

2012 ◽  
Vol 166 (7) ◽  
pp. 2117-2135 ◽  
Author(s):  
Akiko Kojima ◽  
Hirotoshi Kitagawa ◽  
Mariko Omatsu-Kanbe ◽  
Hiroshi Matsuura ◽  
Shuichi Nosaka
Keyword(s):  
Guinea Pig ◽  
Sinoatrial Node ◽  
Inhibitory Effects ◽  
Guinea Pig Heart ◽  
Sinoatrial Node Cells
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