scholarly journals Direct Negative Chronotropic Action of Desflurane on Sinoatrial Node Pacemaker Activity in the Guinea Pig Heart

2014 ◽  
Vol 120 (6) ◽  
pp. 1400-1413 ◽  
Author(s):  
Akiko Kojima ◽  
Yuki Ito ◽  
Hirotoshi Kitagawa ◽  
Hiroshi Matsuura ◽  
Shuichi Nosaka
Keyword(s):  
Heart Rate ◽  
Action Potentials ◽  
Inhibitory Action ◽  
Sinoatrial Node ◽  
Ionic Currents ◽  
Pacemaker Cells ◽  
Chronotropic Action ◽  
Perfused Hearts ◽  
Sinoatrial Node Automaticity

Abstract Background: Desflurane inhalation is associated with sympathetic activation and concomitant increase in heart rate in humans and experimental animals. There is, however, little information concerning the direct effects of desflurane on electrical activity of sinoatrial node pacemaker cells that determines the intrinsic heart rate. Methods: Whole-cell patch-clamp experiments were conducted on guinea pig sinoatrial node pacemaker cells to record spontaneous action potentials and ionic currents contributing to sinoatrial node automaticity, namely, hyperpolarization-activated cation current (If), T-type and L-type Ca2+ currents (ICa,T and ICa,L, respectively), Na+/Ca2+ exchange current (INCX), and rapidly and slowly activating delayed rectifier K+ currents (IKr and IKs, respectively). Electrocardiograms were recorded from ex vivo Langendorff-perfused hearts and in vivo hearts. Results: Desflurane at 6 and 12% decreased spontaneous firing rate of sinoatrial node action potentials by 15.9% (n = 11) and 27.6% (n = 10), respectively, which was associated with 20.4% and 42.5% reductions in diastolic depolarization rate, respectively. Desflurane inhibited If, ICa,T, ICa,L, INCX, and IKs but had little effect on IKr. The negative chronotropic action of desflurane was reasonably well reproduced in sinoatrial node computer model. Desflurane reduced the heart rate in Langendorff-perfused hearts. High concentration (12%) of desflurane inhalation was associated with transient tachycardia, which was totally abolished by pretreatment with the β-adrenergic blocker propranolol. Conclusions: Desflurane has a direct negative chronotropic action on sinoatrial node pacemaking activity, which is mediated by its inhibitory action on multiple ionic currents. This direct inhibitory action of desflurane on sinoatrial node automaticity seems to be counteracted by sympathetic activation associated with desflurane inhalation in vivo.

scholarly journals The Chronotropic Function of Propofol and the Underlying Mechanism in Rabbits

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Wenjie Cheng ◽  
Xiaohua Sun ◽  
Yanfang Liu ◽  
Shiqi Han ◽  
Wanlu Ren
Keyword(s):  
Heart Rate ◽  
Action Potentials ◽  
Sinus Node ◽  
Underlying Mechanism ◽  
Dependent Manner ◽  
Pacemaker Cells ◽  
Concentration Dependent Manner ◽  
Sinoatrial Nodes ◽  
Chronotropic Action ◽  
Dose Dependent

The report of bradycardia caused by propofol is increasing. In the experiment, we investigated the chronotropic function of propofol and the underlying mechanism. Rabbits of both sexes were randomly divided into 4 groups: propofol 5 mg/kg group, 10 mg/kg group, 15 mg/kg group, and sham group. Heart rate and frequency of vagal efferent discharge were recorded before the injection and 0, 0.5, 1, 2, and 10 min after the injection through intravenous mode. Then, their hearts were removed, and sinoatrial nodes were dissected. The action potentials of the sinus node pacemaker cells were recorded by the intracellular glass microelectrode technique, and the sinoatrial (SA) node was exposed to propofol 1, 3, 5, and 10 µM respectively. The action potentials were recorded after the sinoatrial nodes were exposed to each concentration of propofol for 15 min. Our results show that the heart rate significantly decreased, and the vagal efferent discharge was significantly increased at 0, 0.5, 1, and 2 min after the injection, respectively. Besides, as the dose increases, the magnitude of change shows a dose-dependent manner. Propofol exerts a negative chronotropic action on sinoatrial node pacemaker cells. The drug significantly decreased APA, VDD, RPF, and prolonged APD90 in a concentration-dependent manner. These effects may be the main mechanism of propofol-induced bradycardia in clinical study.

Abstract 16515: Differential Functions of HCN1 and HCN4 Pacemaker Channels Within the Sinoatrial Node for the Stable and Precise Beating of the Heart

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Stefanie Fenske ◽  
Vanessa Marks ◽  
Stefanie Koenigsbauer ◽  
Sami I Hassan ◽  
Tilman Ziegler ◽  
...  
Keyword(s):  
Heart Rate ◽  
Mouse Models ◽  
Sinoatrial Node ◽  
Critical Role ◽  
Functional Characterization ◽  
Heart Beat ◽  
Fine Tuning ◽  
Hcn Channels ◽  
Pacemaker Cells

The heart beat is initiated by the generation of spontaneous action potentials in pacemaker cells of the sinoatrial node (SAN) region. The maintenance of a stable heart beat requires mechanisms which protect the SAN pacemaker cells from potential perturbing influences which arise from inside and outside the sinoatrial network. Our previous work suggests that the hyperpolarization-activated cyclic nucleotide gated channel subtype 1 (HCN1) protects against such perturbations and thereby increases the stability, the precision and the safety of the sinoatrial network. Here, we investigate the role of HCN4 channels within this context. Using genetic mouse models deficient for HCN channels as well as mouse models expressing engineered HCN channels, we performed a detailed functional characterization of pacemaker mechanisms in single isolated sinoatrial node cells, explanted beating sinoatrial node preparations, with telemetric in vivo electrocardiography, echocardiography, and in vivo electrophysiology. We provide evidence that HCN4 has a critical role in counteracting and balancing potentially destabilizing effects of the autonomic nervous system on the regulation of the heart rate. Specifically, HCN4 channels smooth the transition of the heart rate to a new equilibrium. Furthermore, we provide evidence that the cAMP- dependent fine tuning of HCN4 channel activity could provide the exact dosage of current to balance and counteract overshooting responses of the heart rate to autonomic regulation. In the absence of such a protecting effect, mice display a brady- tachy syndrome.

ANP has no postsynaptic effect on autonomic regulation of cardiac pacemaker rate in the rat

1993 ◽  
Vol 265 (6) ◽  
pp. H1983-H1987 ◽  
Author(s):  
D. J. Atchison ◽  
P. S. Pennefather ◽  
U. Ackermann
Keyword(s):  
Salt Solution ◽  
Action Potentials ◽  
Sinoatrial Node ◽  
Cardiac Pacemaker ◽  
Pacemaker Activity ◽  
Physiological Salt Solution ◽  
Sprague Dawley ◽  
Pacemaker Cells ◽  
Frequency Of Action Potentials ◽  
The Right

We studied whether atrial natriuretic peptide (ANP) influences sinoatrial node pacemaker activity or whether it modifies the response to activation of postsynaptic autonomic receptors. Male Sprague-Dawley rats were anesthetized with pentobarbital sodium (45 mg/kg). Their hearts were removed quickly and placed in physiological salt solution. The atria were isolated; the right intra-atrial chamber was exposed to allow intracellular recording from sinoatrial node pacemaker cells. The tissue was placed in a temperature-regulated recording chamber and superfused with warmed oxygenated physiological salt solution. With use of standard microelectrode recording techniques, action potentials were recorded from spontaneously depolarizing cells in the presence of muscarine (62.5–500 nM) or norepinephrine (0.1 and 1.0 microM). Muscarine reduced the frequency of action potentials dose dependently, whereas norepinephrine increased their frequency. The addition of ANP (0.1–100 nM) to the superfusion had no effect on the frequency of action potentials during the superfusion of physiological salt solution or in the presence of either muscarine or norepinephrine. We conclude that ANP does not act on cardiac pacemaker cells to modulate the effect of neurotransmitters.

scholarly journals Beating Rate Variability of Isolated Mammal Sinoatrial Node Tissue: Insight Into Its Contribution to Heart Rate Variability

2021 ◽  
Vol 14 ◽  
Author(s):  
Ori Shemla ◽  
Kenta Tsutsui ◽  
Joachim A. Behar ◽  
Yael Yaniv
Keyword(s):  
Heart Rate ◽  
Heart Rate Variability ◽  
Frequency Band ◽  
Sinoatrial Node ◽  
Low Frequency ◽  
Relative Increase ◽  
Test Mouse ◽  
Beating Rate

BackgroundBecause of the complexity of the interaction between the internal pacemaker mechanisms, cell interconnected signals, and interaction with other body systems, study of the role of individual systems must be performed under in vivo and in situ conditions. The in situ approach is valuable when exploring the mechanisms that govern the beating rate and rhythm of the sinoatrial node (SAN), the heart’s primary pacemaker. SAN beating rate changes on a beat-to-beat basis. However, to date, there are no standard methods and tools for beating rate variability (BRV) analysis from electrograms (EGMs) collected from different mammals, and there is no centralized public database with such recordings.MethodsWe used EGM recordings obtained from control SAN tissues of rabbits (n = 9) and mice (n = 30) and from mouse SAN tissues (n = 6) that were exposed to drug intervention. The data were harnessed to develop a beat detector to derive the beat-to-beat interval time series from EGM recordings. We adapted BRV measures from heart rate variability and reported their range for rabbit and mouse.ResultsThe beat detector algorithm performed with 99% accuracy, sensitivity, and positive predictive value on the test (mouse) and validation (rabbit and mouse) sets. Differences in the frequency band cutoff were found between BRV of SAN tissue vs. heart rate variability (HRV) of in vivo recordings. A significant reduction in power spectrum density existed in the high frequency band, and a relative increase was seen in the low and very low frequency bands. In isolated SAN, the larger animal had a slower beating rate but with lower BRV, which contrasted the phenomena reported for in vivo analysis. Thus, the non-linear inverse relationship between the average HR and HRV is not maintained under in situ conditions. The beat detector, BRV measures, and databases were contributed to the open-source PhysioZoo software (available at: https://physiozoo.com/).ConclusionOur approach will enable standardization and reproducibility of BRV analysis in mammals. Different trends were found between beating rate and BRV or HRV in isolated SAN tissue vs. recordings collected under in vivo conditions, respectively, implying a complex interaction between the SAN and the autonomic nervous system in determining HRV in vivo.

scholarly journals Induced Pacemaker Cells Created by In Vivo Somatic Reprogramming: Phenotypic Comparison with Native Sinoatrial Node Cells

2012 ◽  
Vol 102 (3) ◽  
pp. 673a
Author(s):  
Wenbin Liang ◽  
Nidhi Kapoor ◽  
Eduardo Marbán ◽  
Hee Cheol Cho
Keyword(s):  
Sinoatrial Node ◽  
Pacemaker Cells ◽  
Sinoatrial Node Cells

scholarly journals The Pattern of mRNA Expression Is Changed in Sinoatrial Node from Goto-Kakizaki Type 2 Diabetic Rat Heart

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
F. C. Howarth ◽  
M. A. Qureshi ◽  
P. Jayaprakash ◽  
K. Parekh ◽  
M. Oz ◽  
...  
Keyword(s):  
Heart Rate ◽  
Sinoatrial Node ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Cyclic Nucleotide Gated Channels ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Type 2 Diabetic

Background.In vivoexperiments in Goto-Kakizaki (GK) type 2 diabetic rats have demonstrated reductions in heart rate from a young age. The expression of genes encoding more than 70 proteins that are associated with the generation and conduction of electrical activity in the GK sinoatrial node (SAN) have been evaluated to further clarify the molecular basis of the low heart rate.Materials and Methods. Heart rate and expression of genes were evaluated with an extracellular electrode and real-time RT-PCR, respectively. Rats aged 12-13 months were employed in these experiments.Results. Isolated spontaneous heart rate was reduced in GK heart (161 ± 12 bpm) compared to controls (229 ± 11 bpm). There were many differences in expression of mRNA, and some of these differences were of particular interest. Compared to control SAN, expression of some genes were downregulated in GK-SAN: gap junction,Gja1(Cx43),Gja5(Cx40),Gjc1(Cx45), andGjd3(Cx31.9); cell membrane transport,Trpc1(TRPC1) and Trpc6 (TRPC6); hyperpolarization-activated cyclic nucleotide-gated channels,Hcn1(HCN1) andHcn4(HCN4); calcium channels,Cacna1d(Cav1.3),Cacna1g(Cav3.1),Cacna1h(Cav3.2),Cacna2d1(Cavα2δ1),Cacna2d3(Cavα2δ3), andCacng4(Cavγ4); and potassium channels,Kcna2(Kv1.2),Kcna4(Kv1.4),Kcna5(Kv1.5),Kcnb1 (Kv2.1),Kcnd3(Kv4.3),Kcnj2(Kir2.1),Kcnk1(TWIK1),Kcnk5(K2P5.1),Kcnk6(TWIK2), andKcnn2(SK2) whilst others were upregulated in GK-SAN:Ryr2(RYR2) andNppb(BNP).Conclusions. This study provides new insight into the changing expression of genes in the sinoatrial node of diabetic heart.

scholarly journals cAMP-dependent regulation of HCN4 controls the tonic entrainment process in sinoatrial node pacemaker cells

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Stefanie Fenske ◽  
Konstantin Hennis ◽  
René D. Rötzer ◽  
Verena F. Brox ◽  
Elvir Becirovic ◽  
...  
Keyword(s):  
Heart Rate ◽  
Sinoatrial Node ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Mouse Line ◽  
Pacemaker Cells ◽  
Heart Rate Regulation ◽  
Cardiac Phenotype ◽  
Pacemaker Channel ◽  
Central Pacemaker

Abstract It is highly debated how cyclic adenosine monophosphate-dependent regulation (CDR) of the major pacemaker channel HCN4 in the sinoatrial node (SAN) is involved in heart rate regulation by the autonomic nervous system. We addressed this question using a knockin mouse line expressing cyclic adenosine monophosphate-insensitive HCN4 channels. This mouse line displayed a complex cardiac phenotype characterized by sinus dysrhythmia, severe sinus bradycardia, sinus pauses and chronotropic incompetence. Furthermore, the absence of CDR leads to inappropriately enhanced heart rate responses of the SAN to vagal nerve activity in vivo. The mechanism underlying these symptoms can be explained by the presence of nonfiring pacemaker cells. We provide evidence that a tonic and mutual interaction process (tonic entrainment) between firing and nonfiring cells slows down the overall rhythm of the SAN. Most importantly, we show that the proportion of firing cells can be increased by CDR of HCN4 to efficiently oppose enhanced responses to vagal activity. In conclusion, we provide evidence for a novel role of CDR of HCN4 for the central pacemaker process in the sinoatrial node.

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