scholarly journals A Simulation Study on the Pacing and Driving of the Biological Pacemaker

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Yue Zhang ◽  
Lei Zhang ◽  
Yong Wang ◽  
Kuanquan Wang
Keyword(s):  
Calcium Current ◽  
Major Part ◽  
Sodium Current ◽  
Electrical Coupling ◽  
Inward Rectifier ◽  
Ventricular Myocyte ◽  
Ion Currents ◽  
2D Simulation ◽  
Ventricular Cells ◽  
Biological Pacemaker

The research on the biological pacemaker has been very active in recent years. And turning nonautomatic ventricular cells into pacemaking cells is believed to hold the key to making a biological pacemaker. In the study, the inward-rectifier K+ current (IK1) is depressed to induce the automaticity of the ventricular myocyte, and then, the effects of the other membrane ion currents on the automaticity are analyzed. It is discovered that the L-type calcium current (ICaL) plays a major part in the rapid depolarization of the action potential (AP). A small enough ICaL would lead to the failure of the automaticity of the ventricular myocyte. Meanwhile, the background sodium current (IbNa), the background calcium current (IbCa), and the Na+/Ca2+ exchanger current (INaCa) contribute significantly to the slow depolarization, indicating that these currents are the main supplementary power of the pacing induced by depressing IK1, while in the 2D simulation, we find that the weak electrical coupling plays a more important role in the driving of a biological pacemaker.

scholarly journals Electrophysiological Properties of Inferior Olive Neurons: A Compartmental Model

1999 ◽  
Vol 82 (2) ◽  
pp. 804-817 ◽  
Author(s):  
Nicolas Schweighofer ◽  
Kenji Doya ◽  
Mitsuo Kawato
Keyword(s):  
Calcium Current ◽  
Potassium Current ◽  
Inferior Olive ◽  
Sodium Current ◽  
Electrical Coupling ◽  
Biophysical Model ◽  
Delayed Rectifier ◽  
High Threshold ◽  
Electrophysiological Properties

As a step in exploring the functions of the inferior olive, we constructed a biophysical model of the olivary neurons to examine their unique electrophysiological properties. The model consists of two compartments to represent the known distribution of ionic currents across the cell membrane, as well as the dendritic location of the gap junctions and synaptic inputs. The somatic compartment includes a low-threshold calcium current ( I Ca_l), an anomalous inward rectifier current ( I h), a sodium current ( I Na), and a delayed rectifier potassium current ( I K_dr). The dendritic compartment contains a high-threshold calcium current ( I Ca_h), a calcium-dependent potassium current ( I K_Ca), and a current flowing into other cells through electrical coupling ( I c). First, kinetic parameters for these currents were set according to previously reported experimental data. Next, the remaining free parameters were determined to account for both static and spiking properties of single olivary neurons in vitro. We then performed a series of simulated pharmacological experiments using bifurcation analysis and extensive two-parameter searches. Consistent with previous studies, we quantitatively demonstrated the major role of I Ca_l in spiking excitability. In addition, I h had an important modulatory role in the spike generation and period of oscillations, as previously suggested by Bal and McCormick. Finally, we investigated the role of electrical coupling in two coupled spiking cells. Depending on the coupling strength, the hyperpolarization level, and the I Ca_l and I hmodulation, the coupled cells had four different synchronization modes: the cells could be in-phase, phase-shifted, or anti-phase or could exhibit a complex desynchronized spiking mode. Hence these simulation results support the counterintuitive hypothesis that electrical coupling can desynchronize coupled inferior olive cells.

scholarly journals Canine Myocytes Represent a Good Model for Human Ventricular Cells Regarding Their Electrophysiological Properties

2021 ◽  
Vol 14 (8) ◽  
pp. 748
Author(s):  
Péter P. Nánási ◽  
Balázs Horváth ◽  
Fábián Tar ◽  
János Almássy ◽  
Norbert Szentandrássy ◽  
...  
Keyword(s):  
Action Potential ◽  
Time Course ◽  
Laboratory Animals ◽  
Delayed Rectifier ◽  
Ion Currents ◽  
Human Cardiomyocytes ◽  
Ventricular Cells ◽  
Repolarization Reserve ◽  
Electrophysiological Studies ◽  
K Current

Due to the limited availability of healthy human ventricular tissues, the most suitable animal model has to be applied for electrophysiological and pharmacological studies. This can be best identified by studying the properties of ion currents shaping the action potential in the frequently used laboratory animals, such as dogs, rabbits, guinea pigs, or rats, and comparing them to those of human cardiomyocytes. The authors of this article with the experience of three decades of electrophysiological studies, performed in mammalian and human ventricular tissues and isolated cardiomyocytes, summarize their results obtained regarding the major canine and human cardiac ion currents. Accordingly, L-type Ca2+ current (ICa), late Na+ current (INa-late), rapid and slow components of the delayed rectifier K+ current (IKr and IKs, respectively), inward rectifier K+ current (IK1), transient outward K+ current (Ito1), and Na+/Ca2+ exchange current (INCX) were characterized and compared. Importantly, many of these measurements were performed using the action potential voltage clamp technique allowing for visualization of the actual current profiles flowing during the ventricular action potential. Densities and shapes of these ion currents, as well as the action potential configuration, were similar in human and canine ventricular cells, except for the density of IK1 and the recovery kinetics of Ito. IK1 displayed a largely four-fold larger density in canine than human myocytes, and Ito recovery from inactivation displayed a somewhat different time course in the two species. On the basis of these results, it is concluded that canine ventricular cells represent a reasonably good model for human myocytes for electrophysiological studies, however, it must be borne in mind that due to their stronger IK1, the repolarization reserve is more pronounced in canine cells, and moderate differences in the frequency-dependent repolarization patterns can also be anticipated.

Larger late sodium current density as well as greater sensitivities to ATX II and ranolazine in rabbit left atrial than left ventricular myocytes

2014 ◽  
Vol 306 (3) ◽  
pp. H455-H461 ◽  
Author(s):  
Antao Luo ◽  
Jihua Ma ◽  
Yejia Song ◽  
Chunping Qian ◽  
Ying Wu ◽  
...  
Keyword(s):  
Left Atrial ◽  
Ventricular Myocytes ◽  
Sodium Current ◽  
Left Ventricular ◽  
Atrial Myocytes ◽  
Open Probability ◽  
Late Sodium Current ◽  
Ventricular Cells ◽  
Open Time ◽  
Hill Slope

An increase of cardiac late sodium current ( INa.L) is arrhythmogenic in atrial and ventricular tissues, but the densities of INa.L and thus the potential relative contributions of this current to sodium ion (Na+) influx and arrhythmogenesis in atria and ventricles are unclear. In this study, whole-cell and cell-attached patch-clamp techniques were used to measure INa.L in rabbit left atrial and ventricular myocytes under identical conditions. The density of INa.L was 67% greater in left atrial (0.50 ± 0.09 pA/pF, n = 20) than in left ventricular cells (0.30 ± 0.07 pA/pF, n = 27, P < 0.01) when elicited by step pulses from −120 to −20 mV at a rate of 0.2 Hz. Similar results were obtained using step pulses from −90 to −20 mV. Anemone toxin II (ATX II) increased INa.L with an EC50 value of 14 ± 2 nM and a Hill slope of 1.4 ± 0.1 ( n = 9) in atrial myocytes and with an EC50 of 21 ± 5 nM and a Hill slope of 1.2 ± 0.1 ( n = 12) in ventricular myocytes. Na+ channel open probability (but not mean open time) was greater in atrial than in ventricular cells in the absence and presence of ATX II. The INa.L inhibitor ranolazine (3, 6, and 9 μM) reduced INa.L more in atrial than ventricular myocytes in the presence of 40 nM ATX II. In summary, rabbit left atrial myocytes have a greater density of INa.L and higher sensitivities to ATX II and ranolazine than rabbit left ventricular myocytes.

Differential distribution of Kir2.1 and Kir2.3 subunits in canine atrium and ventricle

2002 ◽  
Vol 283 (3) ◽  
pp. H1123-H1133 ◽  
Author(s):  
Peter Melnyk ◽  
Liming Zhang ◽  
Alvin Shrier ◽  
Stanley Nattel
Keyword(s):  
Molecular Mechanisms ◽  
Inward Rectifier ◽  
Differential Distribution ◽  
Atrial Cells ◽  
Ventricular Cells ◽  
Subunit Expression ◽  
Intercalated Disks ◽  
Protein Density ◽  
Cell Data ◽  
Isolated Cell

Ventricular inward rectifier K+ current ( I K1) is substantially larger than atrial, producing functionally important action potential differences. To evaluate possible molecular mechanisms, we recorded I K1 with patch-clamp techniques and studied Kir2.1 and Kir2.3 subunit expression. I K1density was >10-fold larger in the canine ventricle than atrium. Kir2.1 protein expression (Western blot) was 78% greater ( P < 0.01) in the ventricle, but Kir2.3 band density was 228% greater ( P < 0.01) in the atrium. Immunocytochemistry showed transverse tubular localization of Kir2.1 in 89% (17 of 19) of ventricular and 26% (5 of 19, P < 0.0001) of atrial cells. Both exhibited a weakly positive Kir2.1 signal at intercalated disks. Kir2.3 was strongly expressed at the intercalated disks in all cells and in the transverse tubular regions in 78% (14 of 18) of atrial and 22% (4 of 18, P < 0.001) of ventricular cells. Tissue immunohistochemical results qualitatively resembled isolated cell data. We conclude that the expression density and subcellular localization of Kir2.1 and Kir2.3 subunits differ in the canine atrium versus ventricle. Overall protein density differences are insufficient to explain I K1 discrepancies, which may be related to differences in subcellular distribution.

scholarly journals An Antisense Oligonucleotide Against H1 Inhibits the Classical Sodium Current but not I Ca(TTX) in Rat Ventricular Cells

2003 ◽  
Vol 547 (2) ◽  
pp. 435-440 ◽  
Author(s):  
Qun Sha ◽  
Shawn W. Robinson ◽  
Stacey L. McCulle ◽  
Stephen R. Shorofsky ◽  
Paul A. Welling ◽  
...  
Keyword(s):  
Antisense Oligonucleotide ◽  
Sodium Current ◽  
Ventricular Cells

scholarly journals Effect of FMRFamide on voltage-dependent currents in identified centrifugal neurons of the optic lobe of the cuttlefish, Sepia officinalis

2020 ◽  
Author(s):  
Abdesslam Chrachri
Keyword(s):  
Visual Processing ◽  
Calcium Current ◽  
Optic Lobe ◽  
Low Voltage ◽  
Sodium Current ◽  
Calcium Currents ◽  
Delayed Rectifier ◽  
Outward Currents ◽  
Voltage Dependent ◽  
Inward Currents

AbstractWhole-cell patch-clamp recordings from identified centrifugal neurons of the optic lobe in a slice preparation allowed the characterization of five voltage-dependent currents; two outward and three inward currents. The outward currents were; the 4-aminopyridine-sensitive transient potassium or A-current (IA), the TEA-sensitive sustained current or delayed rectifier (IK). The inward currents were; the tetrodotoxin-sensitive transient current or sodium current (INa). The second is the cobalt- and cadmium-sensitive sustained current which is enhanced by barium and blocked by the dihydropyridine antagonist, nifedipine suggesting that it could be the L-type calcium current (ICaL). Finally, another transient inward current, also carried by calcium, but unlike the L-type, this current is activated at more negative potentials and resembles the low-voltage-activated or T-type calcium current (ICaT) of other preparations.Application of the neuropeptide FMRFamide caused a significant attenuation to the peak amplitude of both sodium and sustained calcium currents without any apparent effect on the transient calcium current. Furthermore, FMRFamide also caused a reduction of both outward currents in these centrifugal neurons. The fact that FMRFamide reduced the magnitude of four of five characterized currents could suggest that this neuropeptide may act as a strong inhibitory agent on these neurons.SummaryFMRFamide modulate the ionic currents in identified centrifugal neurons in the optic lobe of cuttlefish: thus, FMRFamide could play a key role in visual processing of these animals.

Abstract 1503: Knockdown of Mog1 Expression Reduces Sodium Currents by Reducing the Trafficking of Cardiac Sodium Channel Na V 1.5 to the Cell Membrane

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Susmita Chakrabarti ◽  
Sandro Yong ◽  
Shin Yoo ◽  
Ling Wu ◽  
Qing Kenneth Wang
Keyword(s):  
Sodium Channel ◽  
Ventricular Myocytes ◽  
Sodium Current ◽  
Expression System ◽  
Heart Association ◽  
Hek293 Cells ◽  
Similar Reduction ◽  
Mammalian Expression ◽  
Ventricular Cells ◽  
Cardiac Sodium Channel

The cardiac sodium channel (Na v 1.5) plays a significant role in cardiac physiology and leads to cardiac arrhythmias and sudden death when mutated. Modulation of Na v 1.5 activity can also arise from changes to accessory subunits or proteins. Our laboratory has recently reported that MOG1, a small protein that is highly conserved from yeast to humans, is a co-factor of Na v 1.5. Increased MOG1 expression has been shown to increase Na v 1.5 current density. In adult mouse ventricular myocytes, these two proteins were found to be co-localized at the intercalated discs. Here, we further characterize the regulatory role of MOG1 using the RNA interference technique. Sodium current was recorded in voltage-clamp mode from a holding potential of −100 mV and activated to −20 mV. In 3-day old mouse neonatal ventricular cells transfected with siRNA against mouse MOG1 decreased sodium current densities (pA/pF) compared to control or scramble siRNA treated cells (−10.2±3.3, n=11 vs. −165±16, n=20 or −117.9±11.7, n=11). A similar reduction in sodium current was observed in mammalian expression system consisting of HEK293 cells stably expressing human Na v 1.5, by transfecting siRNAs against either human or mouse MOG1 (−41.7±8.3, n=7 or, −82.6±9.6, n=7 vs. −130.6±11.5, n=7; −111.5±8.5, n=7, respectively). Immunocytochemistry revealed that the expression of MOG1 and Na v 1.5 were decreased in both HEK and neonatal cells when compared to scramble siRNAs or control groups. These results show that MOG1 is an essential co-factor for Na v 1.5 by way of a channel trafficking. Such interactions between MOG1 and Na v 1.5 suggest that early localization of MOG1 on the membrane of neonatal cardiomyocytes may be necessary for proper localization and the distribution of Na v 1.5 during cardiac development. This research has received full or partial funding support from the American Heart Association, AHA National Center.

The distribution of non-synaptic intercellular junctions during neurone differentiation in the developing spinal cord of the clawed toad

Development ◽  
1975 ◽  
Vol 33 (2) ◽  
pp. 403-417
Author(s):  
Brian P. Hayes ◽  
Alan Roberts
Keyword(s):  
Spinal Cord ◽  
Gap Junctions ◽  
Neural Differentiation ◽  
Electrical Coupling ◽  
Intercellular Junctions ◽  
Ependymal Cells ◽  
Freedom Of Movement ◽  
Ventricular Cells ◽  
Vertebrate Embryos ◽  
Developing Spinal Cord

The distribution of intercellular junctions, other than synapses and their precursors, has beendescribed in the developing spinal cord of Xenopus laevis between the neurula andfree swimming tadpole stages. At the neurocoel, ventricular cells are joined in the apical contactzone by a sequence of junctions which usually has one or more intermediate junctions but often also includes close appositions, gap junctions and desmosomes. This apical complex is more diverse than that reported in other vertebrate embryos and between ependymal cells in the adult central nervous system. Gap junctions are also found between ventricular cells and their processes near the external cord surface. However, no other special junctions occur in this location under the basementlamella which surrounds the cord. Punctate intermediate junctions are generally distributed between undifferentiated and differentiating cells and their processes but were not found in neuropil after stage 28. These results are discussed in relation to cell movements during neural differentiation, possible effects on the freedom of movement of ions and molecules through extracellular pathways in the embryo, and possible intercytoplasmic pathways via gap junctions which may be responsible for the physiologically observed electrical coupling between neural tube cells.

scholarly journals Contribution of L-type Ca2+current to electrical activity in sinoatrial nodal myocytes of rabbits

1999 ◽  
Vol 276 (3) ◽  
pp. H1064-H1077 ◽  
Author(s):  
E. Etienne Verheijck ◽  
Antoni C. G. van Ginneken ◽  
Ronald Wilders ◽  
Lennart N. Bouman
Keyword(s):  
Action Potential ◽  
Calcium Current ◽  
Sodium Current ◽  
Delayed Rectifier ◽  
Current Clamp ◽  
Patch Clamp Technique ◽  
Inward Current ◽  
Delayed Rectifier Current ◽  
Diastolic Depolarization ◽  
Recovery From Inactivation

The role of L-type calcium current ( I Ca,L) in impulse generation was studied in single sinoatrial nodal myocytes of the rabbit, with the use of the amphotericin-perforated patch-clamp technique. Nifedipine, at a concentration of 5 μM, was used to block I Ca,L. At this concentration, nifedipine selectively blocked I Ca,L for 81% without affecting the T-type calcium current ( I Ca,T), the fast sodium current, the delayed rectifier current ( I K), and the hyperpolarization-activated inward current. Furthermore, we did not observe the sustained inward current. The selective action of nifedipine on I Ca,L enabled us to determine the activation threshold of I Ca,L, which was around −60 mV. As nifedipine (5 μM) abolished spontaneous activity, we used a combined voltage- and current-clamp protocol to study the effects of I Ca,L blockade on repolarization and diastolic depolarization. This protocol mimics the action potential such that the repolarization and subsequent diastolic depolarization are studied in current-clamp conditions. Nifedipine significantly decreased action potential duration at 50% repolarization and reduced diastolic depolarization rate over the entire diastole. Evidence was found that recovery from inactivation of I Ca,L occurs during repolarization, which makes I Ca,L available already early in diastole. We conclude that I Ca,L contributes significantly to the net inward current during diastole and can modulate the entire diastolic depolarization.

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