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Physiological Reviews Oct 2005The heart is a rhythmic electromechanical pump, the functioning of which depends on action potential generation and propagation, followed by relaxation and a period of... (Review)
Review
The heart is a rhythmic electromechanical pump, the functioning of which depends on action potential generation and propagation, followed by relaxation and a period of refractoriness until the next impulse is generated. Myocardial action potentials reflect the sequential activation and inactivation of inward (Na(+) and Ca(2+)) and outward (K(+)) current carrying ion channels. In different regions of the heart, action potential waveforms are distinct, owing to differences in Na(+), Ca(2+), and K(+) channel expression, and these differences contribute to the normal, unidirectional propagation of activity and to the generation of normal cardiac rhythms. Changes in channel functioning, resulting from inherited or acquired disease, affect action potential repolarization and can lead to the generation of life-threatening arrhythmias. There is, therefore, considerable interest in understanding the mechanisms that control cardiac repolarization and rhythm generation. Electrophysiological studies have detailed the properties of the Na(+), Ca(2+), and K(+) currents that generate cardiac action potentials, and molecular cloning has revealed a large number of pore forming (alpha) and accessory (beta, delta, and gamma) subunits thought to contribute to the formation of these channels. Considerable progress has been made in defining the functional roles of the various channels and in identifying the alpha-subunits encoding these channels. Much less is known, however, about the functioning of channel accessory subunits and/or posttranslational processing of the channel proteins. It has also become clear that cardiac ion channels function as components of macromolecular complexes, comprising the alpha-subunits, one or more accessory subunit, and a variety of other regulatory proteins. In addition, these macromolecular channel protein complexes appear to interact with the actin cytoskeleton and/or the extracellular matrix, suggesting important functional links between channel complexes, as well as between cardiac structure and electrical functioning. Important areas of future research will be the identification of (all of) the molecular components of functional cardiac ion channels and delineation of the molecular mechanisms involved in regulating the expression and the functioning of these channels in the normal and the diseased myocardium.
Topics: Action Potentials; Animals; Electrophysiology; Heart; Heart Conduction System; Humans; Ion Channels; Myocardial Contraction
PubMed: 16183911
DOI: 10.1152/physrev.00002.2005 -
Neuroscience Bulletin Aug 2012Patch-clamp recording requires direct accessibility of the cell membrane to patch pipettes and allows the investigation of ion channel properties and functions in... (Review)
Review
Patch-clamp recording requires direct accessibility of the cell membrane to patch pipettes and allows the investigation of ion channel properties and functions in specific cellular compartments. The cell body and relatively thick dendrites are the most accessible compartments of a neuron, due to their large diameters and therefore great membrane surface areas. However, axons are normally inaccessible to patch pipettes because of their thin structure; thus studies of axon physiology have long been hampered by the lack of axon recording methods. Recently, a new method of patch-clamp recording has been developed, enabling direct and tight-seal recording from cortical axons. These recordings are performed at the enlarged structure (axonal bleb) formed at the cut end of an axon after slicing procedures. This method has facilitated studies of the mechanisms underlying the generation and propagation of the main output signal, the action potential, and led to the finding that cortical neurons communicate not only in action potential-mediated digital mode but also in membrane potential-dependent analog mode.
Topics: Action Potentials; Animals; Axons; Dendrites; Humans; Membrane Potentials; Neurons; Patch-Clamp Techniques
PubMed: 22833034
DOI: 10.1007/s12264-012-1247-1 -
ENeuro 2018Modeling is a useful tool for investigating various biophysical characteristics of neurons. Recent simulation studies of propagating action potentials (spike conduction)...
Modeling is a useful tool for investigating various biophysical characteristics of neurons. Recent simulation studies of propagating action potentials (spike conduction) along axons include the investigation of neuronal activity evoked by electrical stimulation from implantable prosthetic devices. In contrast to point-neuron simulations, where a large variety of models are readily available, Hodgkin-Huxley-type conductance-based models have been almost the only option for simulating axonal spike conduction, as simpler models cannot faithfully replicate the waveforms of propagating spikes. Since the amount of available physiological data, especially in humans, is usually limited, calibration, and justification of the large number of parameters of a complex model is generally difficult. In addition, not all simulation studies of axons require detailed descriptions of nonlinear ionic dynamics. In this study, we construct a simple model of spike generation and conduction based on the exponential integrate-and-fire model, which can simulate the rapid growth of the membrane potential at spike initiation. In terms of the number of parameters and equations, this model is much more compact than conventional models, but can still reliably simulate spike conduction along myelinated and unmyelinated axons that are stimulated intracellularly or extracellularly. Our simulations of auditory nerve fibers with this new model suggest that, because of the difference in intrinsic membrane properties, the axonal spike conduction of high-frequency nerve fibers is faster than that of low-frequency fibers. The simple model developed in this study can serve as a computationally efficient alternative to more complex models for future studies, including simulations of neuroprosthetic devices.
Topics: Action Potentials; Animals; Axons; Cochlear Nerve; Humans; Models, Neurological; Neural Conduction
PubMed: 30225348
DOI: 10.1523/ENEURO.0112-18.2018 -
Physiological Reports Jan 2022Current understanding of ventricular action potential adaptation to physiological stress is generally based on protocols using non-physiological rates and conditions...
PURPOSE
Current understanding of ventricular action potential adaptation to physiological stress is generally based on protocols using non-physiological rates and conditions isolating rate effects from escalating adrenergic stimulation. To permit refined understanding, ventricular action potentials were assessed across physiological pacing frequencies in the presence and absence of adrenergic stimuli. Isolated and combined effects were analyzed to assess their ability to replicate in-vivo responses.
METHODS
Steady-state action potentials from ventricular myocytes isolated from male Wistar rats (3 months; N = 8 animals) were recorded at 37°C with steady-state pacing at 1, 2, 4, 6, 8 and 10 Hz using whole-cell patch-clamp. Action potential repolarization to 25, 50, 75, 90 and 100% of full repolarization (APD ) was compared before and after 5 nM, 100 nM and 1 µM isoproterenol doses.
RESULTS
A Repeated measures ANOVA found APD shortened with 5 nM isoproterenol infusion by 6-25% (but comparable across doses) (p ≤ 0.03). Pacing frequencies emulating a normal rat heart rate (6 Hz) prolonged APD 23% compared with 1 Hz pacing. Frequencies emulating exercise or stress (10 Hz) shortened APD (29%).
CONCLUSION
These results demonstrate modest action potential shortening in response to adrenergic stimulation and elevations in pacing beyond physiological resting rates. Our findings indicate changes in action potential plateau and late repolarization predominantly underlie simulated exercise responses in the rat heart. This work provides novel action potential reference data and will help model cardiac responses to physiological stimuli in the rat heart via computational techniques.
Topics: Action Potentials; Animals; Heart Ventricles; Isoproterenol; Male; Myocytes, Cardiac; Rats; Rats, Wistar
PubMed: 35076184
DOI: 10.14814/phy2.15166 -
Advances in Physiology Education Dec 2022Since its discovery in the mid-20th century, the Hodgkin-Huxley biophysical model of the squid giant axon's (SGA's) neurophysiology has traditionally served as the basis... (Review)
Review
Since its discovery in the mid-20th century, the Hodgkin-Huxley biophysical model of the squid giant axon's (SGA's) neurophysiology has traditionally served as the basis for the teaching of action potential (AP) dynamics in the physiology classroom. This model teaches that leak conductances set membrane resting potential; that fast, inactivating, voltage-gated sodium channels effect the SGA AP upstroke; and that delayed, rectifying, noninactivating voltage-gated potassium channels carry AP repolarization and the early part of the afterhyperpolarization (AHP). This model serves well to introduce students to the fundamental ideas of resting potential establishment and maintenance, as well as basic principles of AP generation and propagation. Furthermore, the Hodgkin-Huxley SGA model represents an excellent and accessible starting point for discussion of the concept of AP threshold and the role of passive electrical properties of the neuron. Additionally, the introduction of the Hodgkin-Huxley model of the SGA AP permits the integration of physiological principles, as instructors ask students to apply previously studied principles of transporter and channel biophysics to the essential physiological phenomenon of electrical signal conduction. However, both some early observations as well as more recent evidence strongly suggest that this seminal invertebrate model of AP dynamics does not appropriately capture the full story for mammalian axons. We review recent evidence that mammalian axonal nodes of Ranvier repolarize largely (though not exclusively) through the activity of leak potassium-ion (K) conductances carried through two-pore domain (K) channels. We call for changes to physiology textbooks and curricula to highlight this remarkable difference in invertebrate and mammalian AP repolarization mechanisms. Historically, physiology courses have typically taught that action potential repolarization occurs exclusively due to the activation of delayed-rectifier voltage-gated potassium channels. Here, we review and highlight recent evidence that leak potassium channels of the two-pore domain (K) class may largely serve this repolarization role at mammalian nodes of Ranvier. We call for the inclusion of these ideas in physiology curricula at all levels, from high school to graduate school.
Topics: Animals; Humans; Action Potentials; Potassium Channels, Tandem Pore Domain; Membrane Potentials; Potassium Channels, Voltage-Gated; Axons; Potassium; Mammals
PubMed: 36173340
DOI: 10.1152/advan.00171.2021 -
Cell Reports Jan 2021Central nervous system myelination increases action potential conduction velocity. However, it is unclear how myelination is coordinated to ensure the temporally precise...
Central nervous system myelination increases action potential conduction velocity. However, it is unclear how myelination is coordinated to ensure the temporally precise arrival of action potentials and facilitate information processing within cortical and associative circuits. Here, we show that myelin sheaths, supported by mature oligodendrocytes, remain plastic in the adult mouse brain and undergo subtle structural modifications to influence action potential conduction velocity. Repetitive transcranial magnetic stimulation and spatial learning, two stimuli that modify neuronal activity, alter the length of the nodes of Ranvier and the size of the periaxonal space within active brain regions. This change in the axon-glial configuration is independent of oligodendrogenesis and robustly alters action potential conduction velocity. Because aptitude in the spatial learning task was found to correlate with action potential conduction velocity in the fimbria-fornix pathway, modifying the axon-glial configuration may be a mechanism that facilitates learning in the adult mouse brain.
Topics: Action Potentials; Animals; Axons; Brain; Mice
PubMed: 33472075
DOI: 10.1016/j.celrep.2020.108641 -
Scientific Reports Oct 2022Neurons convert external stimuli into action potentials, or spikes, and encode the contained information into the biological nervous system. Despite the complexity of...
Neurons convert external stimuli into action potentials, or spikes, and encode the contained information into the biological nervous system. Despite the complexity of neurons and the synaptic interactions in between, rate models are often adapted to describe neural encoding with modest success. However, it is not clear whether the firing rate, the reciprocal of the time interval between spikes, is sufficient to capture the essential features for the neuronal dynamics. Going beyond the usual relaxation dynamics in Ginzburg-Landau theory for statistical systems, we propose that neural activities can be captured by the U(1) dynamics, integrating the action potential and the "phase" of the neuron together. The gain function of the Hodgkin-Huxley neuron and the corresponding dynamical phase transitions can be described within the U(1) neuron framework. In addition, the phase dependence of the synaptic interactions is illustrated and the mapping to the Kinouchi-Copelli neuron is established. It suggests that the U(1) neuron is the minimal model for single-neuron activities and serves as the building block of the neuronal network for information processing.
Topics: Models, Neurological; Neurons; Action Potentials; Adaptation, Physiological; Computer Simulation
PubMed: 36271115
DOI: 10.1038/s41598-022-22526-0 -
PloS One 2022Fluorescent imaging with voltage- or calcium-sensitive dyes, known as optical mapping, is one of the indispensable modern techniques to study cardiac or neural...
Fluorescent imaging with voltage- or calcium-sensitive dyes, known as optical mapping, is one of the indispensable modern techniques to study cardiac or neural electrophysiology, unsurpassed by temporal and spatial resolution. High-speed CMOS cameras capable of optical registration of action potential propagation are in general very costly. We present a complete solution priced below US$1,000 (including camera and lens) at the moment of publication with an open-source image acquisition and processing software. We demonstrate that the iDS UI-3130CP rev.2 camera we used in this study is capable of 200x200 977 frames per second (FPS) action potential recordings from rodent hearts, with the signal-to-noise-ratio of a conditioned signal of 16 ± 10. A comparison with a specialized MiCAM Ultimate-L camera has shown that signal-to-noise ratio (SNR) while lower is sufficient for accurate measurements of AP waveform, conduction velocity (± 0.04 m/s) and action potential duration (± 7ms) in mouse and rat hearts. We used 4-aminopyridine to prolong the action potential duration in mouse heart, thus demonstrating that the proposed system is adequate for pharmacological studies.
Topics: Action Potentials; Animals; Fluorescent Dyes; Heart; Mice; Rats; Software
PubMed: 35358183
DOI: 10.1371/journal.pone.0259174 -
Cells Feb 2023Purkinje cells (PCs) are the principal cells of the cerebellar cortex and form a central element in the modular organization of the cerebellum. Differentiation of PCs...
Purkinje cells (PCs) are the principal cells of the cerebellar cortex and form a central element in the modular organization of the cerebellum. Differentiation of PCs based on gene expression profiles revealed two subpopulations with distinct connectivity, action potential firing and learning-induced activity changes. However, which basal cell physiological features underlie the differences between these subpopulations and to what extent they integrate input differentially remains largely unclear. Here, we investigate the cellular electrophysiological properties of PC subpopulation in adult and juvenile mice. We found that multiple fundamental cell physiological properties, including membrane resistance and various aspects of the action potential shape, differ between PCs from anterior and nodular lobules. Moreover, the two PC subpopulations also differed in the integration of negative and positive current steps as well as in size of the hyperpolarization-activated current. A comparative analysis in juvenile mice confirmed that most of these lobule-specific differences are already present at pre-weaning ages. Finally, we found that current integration in PCs is input history-dependent for both positive and negative currents, but this is not a distinctive feature between anterior and nodular PCs. Our results support the concept of a fundamental differentiation of PCs subpopulations in terms of cell physiological properties and current integration, yet reveals that history-dependent input processing is consistent across PC subtypes.
Topics: Mice; Animals; Purkinje Cells; Action Potentials; Cerebellum; Learning
PubMed: 36831290
DOI: 10.3390/cells12040623 -
Philosophical Transactions of the Royal... May 2020Action potential generation (spiking) in the neocortex is organized into repeating non-random patterns during both awake experiential states and non-engaged states... (Review)
Review
Action potential generation (spiking) in the neocortex is organized into repeating non-random patterns during both awake experiential states and non-engaged states ranging from inattention to sleep to anaesthesia-and even occur in slice preparations. Repeating patterns in a given population of neurons between states may imply a common means by which cortical networks can be engaged despite brain state changes, but super-imposed on this common firing is a variability that is both specific to ongoing inputs and can be re-shaped by experience. This similarity with specifically induced variance may allow for a range of processes including perception, memory consolidation and network homeostasis. Here, we review how patterned activity in neocortical populations has been studied and what it may imply for a cortex that must be both static and plastic. This article is part of the Theo Murphy meeting issue 'Memory reactivation: replaying events past, present and future'.
Topics: Action Potentials; Animals; Memory; Neocortex; Rats
PubMed: 32248782
DOI: 10.1098/rstb.2019.0233