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  1. Phenomenological analysis of simple ion channel block in large populations of uncoupled cardiomyocytes
    Simitev RD, Al Dawoud A, Aziz MHN, Myles R, Smith GL
    Math Med Biol, 2023 Jun 14;40(2):175-198.
    PMID: 36689769 DOI: 10.1093/imammb/dqad001
    Current understanding of arrhythmia mechanisms and design of anti-arrhythmic drug therapies hinges on the assumption that myocytes from the same region of a single heart have similar, if not identical, action potential waveforms and drug responses. On the contrary, recent experiments reveal significant heterogeneity in uncoupled healthy myocytes both from different hearts as well as from identical regions within a single heart. In this work, a methodology is developed for quantifying the individual electrophysiological properties of large numbers of uncoupled cardiomyocytes under ion channel block in terms of the parameters values of a conceptual fast-slow model of electrical excitability. The approach is applied to a population of nearly 500 rabbit ventricular myocytes for which action potential duration (APD) before and after the application of the drug nifedipine was experimentally measured (Lachaud et al., 2022, Cardiovasc. Res.). To this end, drug action is represented by a multiplicative factor to an effective ion conductance, a closed form asymptotic expression for APD is derived and inverted to determine model parameters as functions of APD and $\varDelta $APD (drug-induced change in APD) for each myocyte. Two free protocol-related quantities are calibrated to experiment using an adaptive-domain procedure based on an original assumption of optimal excitability. The explicit APD expression and the resulting set of model parameter values allow (a) direct evaluation of conditions necessary to maintain fixed APD or $\varDelta $APD, (b) predictions of the proportion of cells remaining excitable after drug application, (c) predictions of stimulus period dependency and (d) predictions of dose-response curves, the latter being in agreement with additional experimental data.
    Matched MeSH terms: Action Potentials/physiology
  2. Ultra-slow oscillations in cortical networks in vitro
    Mok SY, Nadasdy Z, Lim YM, Goh SY
    Neuroscience, 2012 Mar 29;206:17-24.
    PMID: 22266346 DOI: 10.1016/j.neuroscience.2012.01.009
    An ultra-slow oscillation (<0.01 Hz) in the network-wide activity of dissociated cortical networks is described in this article. This slow rhythm is characterized by the recurrence of clusters of large synchronized bursts of activity lasting approximately 1-3 min, separated by an almost equivalent interval of relatively smaller bursts. Such rhythmic activity was detected in cultures starting from the fourth week in vitro. Our analysis revealed that the propagation motifs of constituent bursts were strongly conserved across multiple oscillation cycles, and these motifs were more consistent at the electrode level compared with the neuronal level.
    Matched MeSH terms: Action Potentials/physiology
  3. Fulltext Induced mitochondrial membrane potential for modeling solitonic conduction of electrotonic signals
    Poznanski RR, Cacha LA, Ali J, Rizvi ZH, Yupapin P, Salleh SH, et al.
    PLoS One, 2017;12(9):e0183677.
    PMID: 28880876 DOI: 10.1371/journal.pone.0183677
    A cable model that includes polarization-induced capacitive current is derived for modeling the solitonic conduction of electrotonic potentials in neuronal branchlets with microstructure containing endoplasmic membranes. A solution of the nonlinear cable equation modified for fissured intracellular medium with a source term representing charge 'soakage' is used to show how intracellular capacitive effects of bound electrical charges within mitochondrial membranes can influence electrotonic signals expressed as solitary waves. The elastic collision resulting from a head-on collision of two solitary waves results in localized and non-dispersing electrical solitons created by the nonlinearity of the source term. It has been shown that solitons in neurons with mitochondrial membrane and quasi-electrostatic interactions of charges held by the microstructure (i.e., charge 'soakage') have a slower velocity of propagation compared with solitons in neurons with microstructure, but without endoplasmic membranes. When the equilibrium potential is a small deviation from rest, the nonohmic conductance acts as a leaky channel and the solitons are small compared when the equilibrium potential is large and the outer mitochondrial membrane acts as an amplifier, boosting the amplitude of the endogenously generated solitons. These findings demonstrate a functional role of quasi-electrostatic interactions of bound electrical charges held by microstructure for sustaining solitons with robust self-regulation in their amplitude through changes in the mitochondrial membrane equilibrium potential. The implication of our results indicate that a phenomenological description of ionic current can be successfully modeled with displacement current in Maxwell's equations as a conduction process involving quasi-electrostatic interactions without the inclusion of diffusive current. This is the first study in which solitonic conduction of electrotonic potentials are generated by polarization-induced capacitive current in microstructure and nonohmic mitochondrial membrane current.
    Matched MeSH terms: Action Potentials/physiology*
  4. Assessment of computerized analysis algorithms for one dimension physiologic data with multiple databases
    Lee YK, Bister M, Salleh YM, Blanchfield P
    Annu Int Conf IEEE Eng Med Biol Soc, 2008;2008:5004-7.
    PMID: 19163841 DOI: 10.1109/IEMBS.2008.4650338
    Software technology enables computerized analysis to offer second opinion in various screening and diagnostic tasks to assist the clinicians. Yet, the performance of these computerized methods for medical images is questioned by experts in CAD research, owing to the use of different databases and criteria for evaluating the computer results for comparison. This paper intends to substantiate this statement by illustrating the effects of such issues with the use of 1D physiologic data and multiple databases. For this purpose, the detection of desaturation events in Sp02 and spike events in EEG are used. This is the first time that comparison between different algorithms on a common basis is carried out on an individual effort. The appraisal for all the algorithms is made on the same databases and criteria. It is surprising to find that issues for 2/3D images concur with those found in 1D data here. In evaluating the accuracy of a new algorithm, a single independent database gives results fast. This paper reveals weaknesses of such an approach. It is hoped that the supportive evidence shown here is enough for researchers to innovate a better platform for credibility in reporting performance comparison of computerized analysis algorithms.
    Matched MeSH terms: Action Potentials/physiology*
  5. Evolving spatio-temporal data machines based on the NeuCube neuromorphic framework: Design methodology and selected applications
    Kasabov N, Scott NM, Tu E, Marks S, Sengupta N, Capecci E, et al.
    Neural Netw, 2016 Jun;78:1-14.
    PMID: 26576468 DOI: 10.1016/j.neunet.2015.09.011
    The paper describes a new type of evolving connectionist systems (ECOS) called evolving spatio-temporal data machines based on neuromorphic, brain-like information processing principles (eSTDM). These are multi-modular computer systems designed to deal with large and fast spatio/spectro temporal data using spiking neural networks (SNN) as major processing modules. ECOS and eSTDM in particular can learn incrementally from data streams, can include 'on the fly' new input variables, new output class labels or regression outputs, can continuously adapt their structure and functionality, can be visualised and interpreted for new knowledge discovery and for a better understanding of the data and the processes that generated it. eSTDM can be used for early event prediction due to the ability of the SNN to spike early, before whole input vectors (they were trained on) are presented. A framework for building eSTDM called NeuCube along with a design methodology for building eSTDM using this is presented. The implementation of this framework in MATLAB, Java, and PyNN (Python) is presented. The latter facilitates the use of neuromorphic hardware platforms to run the eSTDM. Selected examples are given of eSTDM for pattern recognition and early event prediction on EEG data, fMRI data, multisensory seismic data, ecological data, climate data, audio-visual data. Future directions are discussed, including extension of the NeuCube framework for building neurogenetic eSTDM and also new applications of eSTDM.
    Matched MeSH terms: Action Potentials/physiology
  6. Effects of demographic and physical factors on nerve conduction study values of healthy subjects in a multi-ethnic Asian population
    Fong SY, Goh KJ, Shahrizaila N, Wong KT, Tan CT
    Muscle Nerve, 2016 08;54(2):244-8.
    PMID: 26790132 DOI: 10.1002/mus.25029
    INTRODUCTION: We investigated the effects of demographic and physical factors on nerve conduction studies (NCS) in a multi-ethnic Asian population.

    METHODS: One hundred sixty-six healthy Malaysians of different ethnicities (51.2% women, aged 21-77 years) underwent NCS using a standard protocol. Correlations of various factors to NCS were determined, and multiple linear regression analysis was used to develop predictive equations for each parameter.

    RESULTS: Age and ethnicity were the commonest independent factors influencing NCS followed by gender, height, weight, and body mass index. Increasing age predicted a reduction in lower limb motor and all sensory nerve action potential amplitudes and decrease in motor and sensory (except sural) conduction velocities. Ethnic Indians had slower motor and sensory conduction velocities in several nerves and also had differences in action potential amplitudes.

    CONCLUSIONS: NCS parameters in multi-ethnic Malaysians were influenced independently by various demographic and physical factors, including ethnicity. Muscle Nerve 54: 244-248, 2016.

    Matched MeSH terms: Action Potentials/physiology*
  7. Reliability of measurement of muscle fiber conduction velocity using surface EMG
    Harba MI, Teng LY
    Front Med Biol Eng, 1999;9(1):31-47.
    PMID: 10354908
    Cross-correlating two surface EMG signals detected at two different locations along the path of flow of action potential enables the measurement of the muscle fiber average conduction velocity in those active motor units monitored by the electrodes. The position of the peak of the cross-correlation function is the time delay between the two signals and hence the velocity may be deduced. The estimated velocity using this technique has been observed previously to depend on the location of the electrodes on the muscle surface. Different locations produced different estimates. In this paper we present a measurement system, analyze its inherent inaccuracies and use it for the purpose of investigating the reliability of measurement of conduction velocity from surface EMG. This system utilizes EMG signals detected at a number of locations on the biceps brachii, when under light tension, to look for any pattern of variations of velocity as a function of location and time. It consists of a multi-electrode unit and a set of eight parallel on-line correlators. The electrode unit and the parallel correlators ensure that these measurements are carried out under the same physical and physiological conditions of the muscle. Further, the same detected signals are used in different measurement configurations to try to understand the reasons behind the observed variations in the estimated velocity. The results obtained seem to suggest that there will always be an unpredictable random component superimposed on the estimated velocity, giving rise to differences between estimates at different locations and differences in estimates with time at the same location. Many factors contribute to this random component, such as the non-homogeneous medium between the muscle fibers and the electrodes, the non-parallel geometry and non-uniform conduction velocity of the fibers, and the physical and physiological conditions of the muscle. While it is not possible to remove this random component completely from the measurement, the user must be aware of its presence and how to reduce its effects.
    Matched MeSH terms: Action Potentials/physiology*
  8. Fulltext Solitonic conduction of electrotonic signals in neuronal branchlets with polarized microstructure
    Poznanski RR, Cacha LA, Al-Wesabi YMS, Ali J, Bahadoran M, Yupapin PP, et al.
    Sci Rep, 2017 May 31;7(1):2746.
    PMID: 28566682 DOI: 10.1038/s41598-017-01849-3
    A model of solitonic conduction in neuronal branchlets with microstructure is presented. The application of cable theory to neurons with microstructure results in a nonlinear cable equation that is solved using a direct method to obtain analytical approximations of traveling wave solutions. It is shown that a linear superposition of two oppositely directed traveling waves demonstrate solitonic interaction: colliding waves can penetrate through each other, and continue fully intact as the exact pulses that entered the collision. These findings indicate that microstructure when polarized can sustain solitary waves that propagate at a constant velocity without attenuation or distortion in the absence of synaptic transmission. Solitonic conduction in a neuronal branchlet arising from polarizability of its microstructure is a novel signaling mode of electrotonic signals in thin processes (<0.5 μm diameter).
    Matched MeSH terms: Action Potentials/physiology
  9. A device to facilitate preparation of high-density neural cell cultures in MEAs
    Mok SY, Lim YM, Goh SY
    J Neurosci Methods, 2009 May 15;179(2):284-91.
    PMID: 19428539 DOI: 10.1016/j.jneumeth.2009.02.009
    A device to facilitate high-density seeding of dissociated neural cells on planar multi-electrode arrays (MEAs) is presented in this paper. The device comprises a metal cover with two concentric cylinders-the outer cylinder fits tightly on to the external diameter of a MEA to hold it in place and an inner cylinder holds a central glass tube for introducing a cell suspension over the electrode area of the MEA. An O-ring is placed at the bottom of the inner cylinder and the glass tube to provide a fluid-tight seal between the glass tube and the MEA electrode surface. The volume of cell suspension in the glass tube is varied according to the desired plating density. After plating, the device can be lifted from the MEA without leaving any residue on the contact surface. The device has enabled us to increase and control the plating density of neural cell suspension with low viability, and to prepare successful primary cultures from cryopreserved neurons and glia. The cultures of cryopreserved dissociated cortical neurons that we have grown in this manner remained spontaneously active over months, exhibited stable development and similar network characteristics as reported by other researchers.
    Matched MeSH terms: Action Potentials/physiology
  10. The role of neuron-glia interactions in the emergence of ultra-slow oscillations
    Chan SC, Mok SY, Ng DW, Goh SY
    Biol Cybern, 2017 Dec;111(5-6):459-472.
    PMID: 29128889 DOI: 10.1007/s00422-017-0740-z
    Ultra-slow cortical oscillatory activity of 1-100 mHz has been recorded in human by electroencephalography and in dissociated cultures of cortical rat neurons, but the underlying mechanisms remain to be elucidated. This study presents a computational model of ultra-slow oscillatory activity based on the interaction between neurons and astrocytes. We predict that the frequency of these oscillations closely depends on activation of astrocytes in the network, which is reflected by oscillations of their intracellular calcium concentrations with periods between tens of seconds and minutes. An increase of intracellular calcium in astrocytes triggers the release of adenosine triphosphate from these cells which may alter transmission at nearby synapses by increasing or decreasing neurotransmitter release. These results provide theoretical support for the emerging awareness of astrocytes as active players in the regulation of neural activity and identify neuron-astrocyte interactions as a potential primary mechanism for the emergence of ultra-slow cortical oscillations.
    Matched MeSH terms: Action Potentials/physiology*
  11. Fulltext Effects of ageing on pro-arrhythmic ventricular phenotypes in incrementally paced murine Pgc-1β -/- hearts
    Ahmad S, Valli H, Edling CE, Grace AA, Jeevaratnam K, Huang CL
    Pflugers Arch, 2017 Dec;469(12):1579-1590.
    PMID: 28821956 DOI: 10.1007/s00424-017-2054-3
    A range of chronic clinical conditions accompany cardiomyocyte energetic dysfunction and constitute independent risk factors for cardiac arrhythmia. We investigated pro-arrhythmic and arrhythmic phenotypes in energetically deficient C57BL mice with genetic ablation of the mitochondrial promoter peroxisome proliferator-activated receptor-γ coactivator-1β (Pgc-1β), a known model of ventricular arrhythmia. Pro-arrhythmic and cellular action potential (AP) characteristics were compared in intact Langendorff-perfused hearts from young (12-16 week) and aged (> 52 week), wild-type (WT) and Pgc-1β -/- mice. Simultaneous electrocardiographic and intracellular microelectrode recordings were made through successive trains of 100 regular stimuli at progressively incremented heart rates. Aged Pgc-1β -/- hearts displayed an increased incidence of arrhythmia compared to other groups. Young and aged Pgc-1β -/- hearts showed higher incidences of alternans in both AP activation (maximum AP upshoot velocity (dV/dt)max and latency), recovery (action potential duration (APD90) and resting membrane potential (RMP) characteristics compared to WT hearts. This was particularly apparent at lower pacing frequencies. These findings accompanied reduced (dV/dt)max and increased AP latency values in the Pgc-1β -/- hearts. APs observed prior to termination of the protocol showed lower (dV/dt)max and longer AP latencies, but indistinguishable APD90 and RMPs in arrhythmic compared to those in non-arrhythmic hearts. APD restitution analysis showed that Pgc-1β -/- and WT hearts showed similar limiting gradients. However, Pgc-1β -/- hearts had shortened plateau AP wavelengths, particularly in aged Pgc-1β -/- hearts. Pgc-1β -/- hearts therefore show pro-arrhythmic instabilities attributable to altered AP conduction and activation rather than recovery characteristics.
    Matched MeSH terms: Action Potentials/physiology
  12. Role of supraspinal vasopressin neurones in the effects of atrial natriuretic peptide on sympathetic nerve activity
    Yusof AP, Yusoff NH, Suhaimi FW, Coote JH
    Auton Neurosci, 2009 Jun 15;148(1-2):50-4.
    PMID: 19349212 DOI: 10.1016/j.autneu.2009.03.005
    The aim of the present study was to determine if paraventricular-spinal vasopressin neurones participate in the sympatho-inhibitory effects of systemically administered atrial natriuretic peptide (ANP) on renal sympathetic nerve activity (RSNA). Experiments were carried out on male Sprague-Dawley rats anesthetized with 1.3 g/kg urethane. Changes in mean arterial pressure (mm Hg), heart rate (beats per minute) and RSNA (%) were measured following intravenous bolus administration of ANP (250 ng, 500 ng and 5 microg). Intrathecal application of selective V 1a receptor antagonist was performed to test for the involvement of supraspinal vasopressin pathways in mediating the effect on sympathetic outflow evoked by intravenous ANP administration. The results obtained demonstrated that both low and high doses of ANP caused renal sympathoinhibition (250 ng; - 7.5 +/- 1%, 500 ng; - 14.2 +/- 1%, 5 microg; - 16.4 +/- 2%), concomitant with vasodilation and bradycardia. After spinal vasopressin receptor blockade, the inhibitory effects of ANP were prevented and there was a small renal sympatho-excitation (250 ng; + 1.7 +/- 0.2%, 500 ng; + 6.1 +/- 0.03%, 5 microg; + 8.0 +/- 0.03%, P < 0.05). Therefore, the renal sympathetic nerve inhibition elicited by circulating ANP is dependent on the efficacy of a well established supraspinal vasopressin pathway. Since supraspinal vasopressin neurones without exception excite renal sympathetic neurones, it is suggested that ANP elicits this effect by activating cardiac vagal afferents that inhibit the spinally projecting vasopressin neurones at their origin in the paraventricular nucleus of the hypothalamus.
    Matched MeSH terms: Action Potentials/physiology
  13. Fulltext In vitro differentiation between oxytocin- and vasopressin-secreting magnocellular neurons requires more than one experimental criterion
    da Silva MP, Merino RM, Mecawi AS, Moraes DJ, Varanda WA
    Mol Cell Endocrinol, 2015 Jan 15;400:102-11.
    PMID: 25451978 DOI: 10.1016/j.mce.2014.11.004
    The phenotypic differentiation between oxytocin (OT)- and vasopressin (VP)-secreting magnocellular neurosecretory cells (MNCs) from the supraoptic nucleus is relevant to understanding how several physiological and pharmacological challenges affect their electrical activity. Although the firing patterns of OT and VP neurons, both in vivo and in vitro, may appear different from each other, much is assumed about their characteristics. These assumptions make it practically impossible to obtain a confident phenotypic differentiation based exclusively on the firing patterns. The presence of a sustained outward rectifying potassium current (SOR) and/or an inward rectifying hyperpolarization-activated current (IR), which are presumably present in OT neurons and absent in VP neurons, has been used to distinguish between the two types of MNCs in the past. In this study, we aimed to analyze the accuracy of the phenotypic discrimination of MNCs based on the presence of rectifying currents using comparisons with the molecular phenotype of the cells, as determined by single-cell RT-qPCR and immunohistochemistry. Our results demonstrated that the phenotypes classified according to the electrophysiological protocol in brain slices do not match their molecular counterparts because vasopressinergic and intermediate neurons also exhibit both outward and inward rectifying currents. In addition, we also show that MNCs can change the relative proportion of each cell phenotype when the system is challenged by chronic hypertonicity (70% water restriction for 7 days). We conclude that for in vitro preparations, the combination of mRNA detection and immunohistochemistry seems to be preferable when trying to characterize a single MNC phenotype.
    Matched MeSH terms: Action Potentials/physiology*
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