Interbeat interval modulation in the sinoatrial node as a result of membrane current stochasticity-a theoretical and numerical study.


:A single isolated sinoatrial pacemaker cell presents intrinsic interbeat interval (IBI) variability that is believed to result from the stochastic characteristics of the opening and closing processes of membrane ion channels. To our knowledge, a novel mathematical framework was developed in this work to address the effect of current fluctuations on the IBIs of sinoatrial pacemaker cells. Using statistical modeling and employing the Fokker-Planck formalism, our mathematical analysis suggests that increased stochastic current fluctuation variance linearly increases the slope of phase-4 depolarization, hence the rate of activations. Single-cell and two-dimensional computerized numerical modeling of the sinoatrial node was conducted to validate the theoretical predictions using established ionic kinetics of the rabbit pacemaker and atrial cells. Our models also provide, to our knowledge, a novel complementary or alternative explanation to recent experimental observations showing a strong reduction in the mean IBI of Cx30 deficient mice in comparison to wild-types, not fully explicable by the effects of intercellular decoupling.


Biophys J


Biophysical journal


Dvir H,Zlochiver S




Has Abstract


2015-03-10 00:00:00














  • Different types of cell-to-cell connections mediated by nanotubular structures.

    abstract::Communication between cells is crucial for proper functioning of multicellular organisms. The recently discovered membranous tubes, named tunneling nanotubes, that directly bridge neighboring cells may offer a very specific and effective way of intercellular communication. Our experiments on RT4 and T24 urothelial cel...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Veranic P,Lokar M,Schütz GJ,Weghuber J,Wieser S,Hägerstrand H,Kralj-Iglic V,Iglic A

    更新日期:2008-11-01 00:00:00

  • Mechanisms of cardiac cell excitation with premature monophasic and biphasic field stimuli: a model study.

    abstract::The mechanisms by which extracellular electric field stimuli induce the (re)excitation of cardiac cells in various stages of refractoriness are still not well understood. We modeled the interactions between an isolated cardiac cell and imposed extracellular electric fields to determine the mechanisms by which relative...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Fishler MG,Sobie EA,Thakor NV,Tung L

    更新日期:1996-03-01 00:00:00

  • Mechanisms of cation permeation in cardiac sodium channel: description by dynamic pore model.

    abstract::The selective permeability to monovalent metal cations, as well as the relationship between cation permeation and gating kinetics, was investigated for native tetrodotoxin-insensitive Na-channels in guinea pig ventricular myocytes using the whole-cell patch clamp technique. By the measurement of inward unidirectional ...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Kurata Y,Sato R,Hisatome I,Imanishi S

    更新日期:1999-10-01 00:00:00

  • A mathematical model of cardiocyte Ca(2+) dynamics with a novel representation of sarcoplasmic reticular Ca(2+) control.

    abstract::Cardiac contraction and relaxation dynamics result from a set of simultaneously interacting Ca(2+) regulatory mechanisms. In this study, cardiocyte Ca(2+) dynamics were modeled using a set of six differential equations that were based on theories, equations, and parameters described in previous studies. Among the uniq...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Snyder SM,Palmer BM,Moore RL

    更新日期:2000-07-01 00:00:00

  • X-rays and nitrogen mustard: independent action in Chinese hamster cells.

    abstract::We have studied the combined effects of X-irradiation and nitrogen mustard treatment on the colony-forming ability of Chinese hamster cells. In contrast to X-irradiation, nitrogen mustard acting by itself yields an exponential dose-effect relationship. Moreover, whether delivered in immediate sequence or after varying...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Sakamoto K,Elkind MM

    更新日期:1969-09-01 00:00:00

  • Photoreactivation and excision repair of ultraviolet radiation-injured DNA in primary embryonic chick cells.

    abstract::Primary embryonic chick cells have been evaluated on the basis of their capacity to repair photochemical lesions produced in the deoxyribonucleic acid (DNA) by ultraviolet (UV) radiation. The fate of one prominent class of UV photoproducts, cyclobutane pyrimidine dimers, was monitored by an in vitro enzymatic assay. U...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Paterson MC,Lohman PH,de Weerd-Kastelein EA,Westerveld A

    更新日期:1974-06-01 00:00:00

  • Elementary events underlying voltage-dependent G-protein inhibition of N-type calcium channels.

    abstract::Voltage-dependent G-protein inhibition of N-type calcium channels reduces presynaptic calcium entry, sharply attenuating neurotransmitter release. Studies in neurons demonstrate that G-proteins have multiple modulatory effects on N-type channels. The observed changes may reflect genuine complexity in G-protein action ...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Patil PG,de Leon M,Reed RR,Dubel S,Snutch TP,Yue DT

    更新日期:1996-11-01 00:00:00

  • Explicit spatiotemporal simulation of receptor-G protein coupling in rod cell disk membranes.

    abstract::Dim-light vision is mediated by retinal rod cells. Rhodopsin (R), a G-protein-coupled receptor, switches to its active form (R(∗)) in response to absorbing a single photon and activates multiple copies of the G-protein transducin (G) that trigger further downstream reactions of the phototransduction cascade. The class...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Schöneberg J,Heck M,Hofmann KP,Noé F

    更新日期:2014-09-02 00:00:00

  • Is there a conserved interaction between cardiolipin and the type II bacterial reaction center?

    abstract::In a recent publication, the structural details of an interaction between the Rhodobacter sphaeroides reaction center and the anionic phospholipid diphosphatidyl glycerol (cardiolipin) were described (K. E. McAuley, P. K. Fyfe, J. P. Ridge, N. W. Isaacs, R. J. Cogdell, and M. R. Jones, 1999, Proc. Natl. Acad. Sci. U.S...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Wakeham MC,Sessions RB,Jones MR,Fyfe PK

    更新日期:2001-03-01 00:00:00

  • Optimal identification of biochemical reaction networks.

    abstract::Advances in biotechnology and computer science are providing the possibility to construct mathematical models for complex biological networks and systematically understand their properties. Traditional network identification approaches, however, cannot accurately recover the model parameters from the noisy laboratory ...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Feng XJ,Rabitz H

    更新日期:2004-03-01 00:00:00

  • Anesthetic inhibition of firefly luciferase, a protein model for general anesthesia, does not exhibit pressure reversal.

    abstract::The surprising observation that pressures of the order of 150 atmospheres can restore consciousness to an anesthetized animal has long been central to theories of the molecular mechanisms underlying general anesthesia. We have constructed a high-pressure gas chamber to test for "pressure reversal" of the best availabl...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Moss GW,Lieb WR,Franks NP

    更新日期:1991-12-01 00:00:00

  • Polarized infrared spectroscopy of oriented purple membrane.

    abstract::Polarized Fourier transform infrared spectroscopy has been used to study the structure of purple membrane from Halobacterium halobium. Membranes were oriented by drying a suspension of membrane fragments onto Irtran-4 slides. Dichroism measurements of the amide I, II and A peaks were used to find the average spatial o...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Rothschild KJ,Clark NA

    更新日期:1979-03-01 00:00:00

  • Role of Inverse-Cone-Shape Lipids in Temperature-Controlled Self-Reproduction of Binary Vesicles.

    abstract::We investigate a temperature-driven recursive division of binary giant unilamellar vesicles (GUVs). During the heating step of the heating-cooling cycle, the spherical mother vesicle deforms to a budded limiting shape using up the excess area produced by the chain melting of the lipids and then splits off into two dau...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Jimbo T,Sakuma Y,Urakami N,Ziherl P,Imai M

    更新日期:2016-04-12 00:00:00

  • Models of beta-amyloid ion channels in the membrane suggest that channel formation in the bilayer is a dynamic process.

    abstract::Here we model the Alzheimer beta-peptide ion channel with the goal of obtaining insight into the mechanism of amyloid toxicity. The models are built based on NMR data of the oligomers, with the universal U-shaped (strand-turn-strand) motif. After 30-ns simulations in the bilayer, the channel dimensions, shapes and sub...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Jang H,Zheng J,Nussinov R

    更新日期:2007-09-15 00:00:00

  • Molecular dynamics study of the energetic, mechanistic, and structural implications of a closed phosphate tube in ncd.

    abstract::The switch 1 region of myosin forms a lid over the nucleotide phosphates as part of a structure known as the phosphate-tube. The homologous region in kinesin-family motors is more open, not interacting with the nucleotide. We used molecular dynamics (MD) simulations to examine a possible displacement of switch 1 of th...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Minehardt TJ,Cooke R,Pate E,Kollman PA

    更新日期:2001-03-01 00:00:00

  • Torque generation mechanism of F1-ATPase upon NTP binding.

    abstract::Molecular machines fueled by NTP play pivotal roles in a wide range of cellular activities. One common feature among NTP-driven molecular machines is that NTP binding is a major force-generating step among the elementary reaction steps comprising NTP hydrolysis. To understand the mechanism in detail,in this study, we ...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Arai HC,Yukawa A,Iwatate RJ,Kamiya M,Watanabe R,Urano Y,Noji H

    更新日期:2014-07-01 00:00:00

  • Computer simulations of de novo designed helical proteins.

    abstract::In the context of reduced protein models, Monte Carlo simulations of three de novo designed helical proteins (four-member helical bundle) were performed. At low temperatures, for all proteins under consideration, protein-like folds having different topologies were obtained from random starting conformations. These sim...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Sikorski A,Kolinski A,Skolnick J

    更新日期:1998-07-01 00:00:00

  • From atomic to mesoscopic descriptions of the internal dynamics of DNA.

    abstract::An analysis of four 1-ns molecular dynamics trajectories for two different 15-bp oligonucleotides is presented. Our aim is to show which groups of atoms can be treated as rigid bodies within a bead representation of DNA, independently of the base sequence and for any conformations belonging to the A/B family. Five mod...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Bruant N,Flatters D,Lavery R,Genest D

    更新日期:1999-11-01 00:00:00

  • Fiber orientation and ejection fraction in the human left ventricle.

    abstract::Fiber orientation and ventricular geometry are incorporated in a mathematical model for ejection fraction of the human left ventricle. The inadequacy of circularly oriented or "constrictor" fibers to explain high ejection fractions of cylindrical, spherical, or ellipsoidal reference ventricles is demonstrated. A class...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Sallin EA

    更新日期:1969-07-01 00:00:00

  • Tissue-specific mathematical models of slow wave entrainment in wild-type and 5-HT(2B) knockout mice with altered interstitial cells of Cajal networks.

    abstract::Gastrointestinal slow waves are generated within networks of interstitial cells of Cajal (ICCs). In the intact tissue, slow waves are entrained to neighboring ICCs with higher intrinsic frequencies, leading to active propagation of slow waves. Degradation of ICC networks in humans is associated with motility disorders...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Du P,O'Grady G,Gibbons SJ,Yassi R,Lees-Green R,Farrugia G,Cheng LK,Pullan AJ

    更新日期:2010-05-19 00:00:00

  • Initial conformational changes of human transthyretin under partially denaturing conditions.

    abstract::Human transthyretin (TTR) is an amyloidogenic protein. The pathway of TTR amyloid formation has been proposed based on lines of evidence: TTR tetramer first dissociates into native monomers, which is shown to be a rate-limiting step in the formation of fibrils. Subsequently, the monomeric species partially unfold to f...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Yang M,Lei M,Bruschweiler R,Huo S

    更新日期:2005-07-01 00:00:00

  • Adaptation in cones. A general model.

    abstract::Three features appear to characterize steady-state light adaptation in vertebrate cone photoreceptors: (a) the shape of the "log intensity-response" curve at different levels of adaptation is the same, the only change with adaptation is in the position of the point on the curve about which the cones operate; (b) at hi...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Dawis SM,Purple RL

    更新日期:1982-08-01 00:00:00

  • Trans-unsaturated lipid dynamics: modulation of dielaidoylphosphatidylcholine acyl chain motion by ethanol.

    abstract::Acyl chain dynamics of the trans-unsaturated lipid, dielaidoylphosphatidylcholine (DEPC), were studied by conventional and saturation transfer electron paramagnetic resonance spectroscopy of aqueous dispersions of DEPC spin labeled with lecithins having doxyl groups at positions 5, 10, and 14 on the sn-2 chain. The ge...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Dalton LA,Miller KW

    更新日期:1993-10-01 00:00:00

  • A Thermodynamic Model for Genome Packaging in Hepatitis B Virus.

    abstract::Understanding the fundamentals of genome packaging in viral capsids is important for finding effective antiviral strategies and for utilizing benign viral particles for gene therapy. While the structure of encapsidated genomic materials has been routinely characterized with experimental techniques such as cryo-electro...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Kim J,Wu J

    更新日期:2015-10-20 00:00:00

  • Physiological pathway of magnesium influx in rat ventricular myocytes.

    abstract::Cytoplasmic free Mg(2+) concentration ([Mg(2+)]i) was measured in rat ventricular myocytes with a fluorescent indicator furaptra (mag-fura-2) introduced by AM-loading. By incubation of the cells in a high-K(+) (Ca(2+)- and Mg(2+)-free) solution, [Mg(2+)]i decreased from ? 0.9 mM to 0.2 to 0.5 mM. The lowered [Mg(2+)]i...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Tashiro M,Inoue H,Konishi M

    更新日期:2014-11-04 00:00:00

  • An information-based approach to change-point analysis with applications to biophysics and cell biology.

    abstract::This article describes the application of a change-point algorithm to the analysis of stochastic signals in biological systems whose underlying state dynamics consist of transitions between discrete states. Applications of this analysis include molecular-motor stepping, fluorophore bleaching, electrophysiology, partic...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Wiggins PA

    更新日期:2015-07-21 00:00:00

  • An analysis of the membrane potential along a clamped squid axon.

    abstract::A partially depolarized squid axon membrane is assumed to have a quasi-steady state negative resistance, the membrane potential is clamped at one point, and a distribution of potential along the axon is obtained from the cable equation. Nominal experimental values of -2 ohm cm(2) for the membrane and 6 ohm cm(2) for t...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: COLE KS

    更新日期:1961-05-01 00:00:00

  • Interaction of the influenza hemagglutinin fusion peptide with lipid bilayers: area expansion and permeation.

    abstract::Fusion is a crucial event in the infection of animal cells by enveloped viruses (e.g., HIV or influenza). Viral fusion is mediated by glycoproteins, spanning the viral envelope, which attach to a membrane surface and induce fusion of the viral envelope to the cellular membrane. Influenza fusion protein (hemagglutinin)...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Longo ML,Waring AJ,Hammer DA

    更新日期:1997-09-01 00:00:00

  • Routes to DNA accessibility: alternative pathways for nucleosome unwinding.

    abstract::The dynamic packaging of DNA into chromatin is a key determinant of eukaryotic gene regulation and epigenetic inheritance. Nucleosomes are the basic unit of chromatin, and therefore the accessible states of the nucleosome must be the starting point for mechanistic models regarding these essential processes. Although t...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Schlingman DJ,Mack AH,Kamenetska M,Mochrie SGJ,Regan L

    更新日期:2014-07-15 00:00:00

  • Pulsed interleaved excitation.

    abstract::In this article, we demonstrate the new method of pulsed interleaved excitation (PIE), which can be used to extend the capabilities of multiple-color fluorescence imaging, fluorescence cross-correlation spectroscopy (FCCS), and single-pair fluorescence resonance energy transfer (spFRET) measurements. In PIE, multiple ...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Müller BK,Zaychikov E,Bräuchle C,Lamb DC

    更新日期:2005-11-01 00:00:00