Linear transformations extract parameters of ionic currents and action potential features from pseudo-ECG in cardiomyocyte models

We studied the effects of tetrodotoxin (TTX) and lidocaine on transmembrane action potentials and ionic currents in dog isolated ventricular myocytes. TTX (0.1-1 x 10(-5) M) and lidocaine (0.5-2 x 10(-5) M) decreased action potential duration, but only TTX decreased the maximum rate of depolarization (Vmax). Both TTX (1-2 x 10(-5) M) and lidocaine (2-5 x 10(-5) M) blocked a slowly inactivating toward current in the plateau voltage range. The voltage- and time-dependent characteristics of this current are virtually identical to those described in Purkinje fibers for the slowly inactivating inward Na+ current. In addition, TTX abolished the outward shift in net current at plateau potentials caused by lidocaine alone. Lidocaine had no detectable effect on the slow inward Ca2+ current and the inward K+ current rectifier, Ia. Our results indicate that 1) there is a slowly inactivating inward Na+ current in ventricular cells similar in time, voltage, and TTX sensitivity to that described in Purkinje fibers; 2) both TTX and lidocaine shorten ventricular action potentials by reducing this slowly inactivating Na+ current; 3) lidocaine has no additional actions on other ionic currents that contribute to its ability to abbreviate ventricular action potentials; and 4) although both agents shorten the action potential by the same mechanism, only TTX reduces Vmax. This last point suggests that TTX produces tonic block of Na+ current, whereas lidocaine may produce state-dependent Na+ channel block, namely, blockade of Na+ current only after Na+ channels have already been opened (inactivated-state block).

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Understanding the electrical behavior of the action potential in terms of elementary electrical sources

AJP Advances in Physiology Education ◽

10.1152/advan.00130.2014 ◽

2015 ◽

Vol 39 (1) ◽

pp. 15-26 ◽

Cited By ~ 6

Author(s):

Javier Rodriguez-Falces

Keyword(s):

Action Potential ◽

Action Potentials ◽

Present Report ◽

Electrical Potential ◽

Ionic Currents ◽

New Approach ◽

Electrical Potentials ◽

Proposed Model ◽

Ionic Mechanisms ◽

Human Electrophysiology

A concept of major importance in human electrophysiology studies is the process by which activation of an excitable cell results in a rapid rise and fall of the electrical membrane potential, the so-called action potential. Hodgkin and Huxley proposed a model to explain the ionic mechanisms underlying the formation of action potentials. However, this model is unsuitably complex for teaching purposes. In addition, the Hodgkin and Huxley approach describes the shape of the action potential only in terms of ionic currents, i.e., it is unable to explain the electrical significance of the action potential or describe the electrical field arising from this source using basic concepts of electromagnetic theory. The goal of the present report was to propose a new model to describe the electrical behaviour of the action potential in terms of elementary electrical sources (in particular, dipoles). The efficacy of this model was tested through a closed-book written exam. The proposed model increased the ability of students to appreciate the distributed character of the action potential and also to recognize that this source spreads out along the fiber as function of space. In addition, the new approach allowed students to realize that the amplitude and sign of the extracellular electrical potential arising from the action potential are determined by the spatial derivative of this intracellular source. The proposed model, which incorporates intuitive graphical representations, has improved students' understanding of the electrical potentials generated by bioelectrical sources and has heightened their interest in bioelectricity.

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Size and Ionic Currents of Unexcitable Cells Coupled to Cardiomyocytes Distinctly Modulate Cardiac Action Potential Shape and Pacemaking Activity in Micropatterned Cell Pairs

Circulation Arrhythmia and Electrophysiology ◽

10.1161/circep.111.969329 ◽

2012 ◽

Vol 5 (4) ◽

pp. 821-830 ◽

Cited By ~ 16

Author(s):

Luke C. McSpadden ◽

Hung Nguyen ◽

Nenad Bursac

Keyword(s):

Action Potential ◽

Ionic Currents ◽

Cardiac Action Potential ◽

Cardiac Action ◽

Potential Shape ◽

Action Potential Shape

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On the Origin of the Extracellular Action Potential Waveform: A Modeling Study

Journal of Neurophysiology ◽

10.1152/jn.00979.2005 ◽

2006 ◽

Vol 95 (5) ◽

pp. 3113-3128 ◽

Cited By ~ 341

Author(s):

Carl Gold ◽

Darrell A. Henze ◽

Christof Koch ◽

György Buzsáki

Keyword(s):

Action Potential ◽

Pyramidal Neurons ◽

Ionic Currents ◽

Dendritic Morphology ◽

Electrode Position ◽

Unit Recording ◽

Extracellular Recordings ◽

Ca1 Pyramidal Neurons ◽

Varied Composition

Although extracellular unit recording is typically used for the detection of spike occurrences, it also has the theoretical ability to report about what are typically considered intracellular features of the action potential. We address this theoretical ability by developing a model system that captures features of experimentally recorded simultaneous intracellular and extracellular recordings of CA1 pyramidal neurons. We use the line source approximation method of Holt and Koch to model the extracellular action potential (EAP) voltage resulting from the spiking activity of individual neurons. We compare the simultaneous intracellular and extracellular recordings of CA1 pyramidal neurons recorded in vivo with model predictions for the same cells reconstructed and simulated with compartmental models. The model accurately reproduces both the waveform and the amplitude of the EAPs, although it was difficult to achieve simultaneous good matches on both the intracellular and extracellular waveforms. This suggests that accounting for the EAP waveform provides a considerable constraint on the overall model. The developed model explains how and why the waveform varies with electrode position relative to the recorded cell. Interestingly, each cell's dendritic morphology had very little impact on the EAP waveform. The model also demonstrates that the varied composition of ionic currents in different cells is reflected in the features of the EAP.

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Activity-dependent enhancement of presynaptic facilitation provides a cellular mechanism for the temporal specificity of classical conditioning in Aplysia.

Learning & Memory ◽

10.1101/lm.1.4.243 ◽

1994 ◽

Vol 1 (4) ◽

pp. 243-257

Author(s):

G A Clark ◽

R D Hawkins ◽

E R Kandel

Keyword(s):

Action Potential ◽

Classical Conditioning ◽

Sensory Neurons ◽

Cell Activity ◽

Critical Time ◽

Ionic Currents ◽

Temporal Specificity ◽

The Us ◽

Activity Dependent ◽

Presynaptic Facilitation

A hallmark of many forms of classical conditioning is a precise temporal specificity: Learning is optimal when the conditioned stimulus (CS) slightly precedes the unconditioned stimulus (US), but the learning is degraded at longer or backward intervals, consistent with the notion that conditioning involves learning about predictive relationships in the environment. To further examine the cellular mechanisms contributing to the temporal specificity of classical conditioning of the siphon-withdrawal response in Aplysia, we paired action potential activity in siphon sensory neurons (the neural CS) with tail nerve shock (the US) at three critical time points. We found that CS-US pairings at short (0.5 sec) forward intervals produced greater synaptic facilitation at sensorimotor connections than did either 0.5-sec backward pairings or longer (5 sec) forward pairings, as reflected in a differential increase in both the amplitude and rate of rise of the synaptic potential. In the same preparations, forward pairings also differentially reduced the sensory neuron afterhyperpolarization relative to backward pairings, suggesting that changes in synaptic efficacy were accompanied by temporally specific changes in ionic currents in the sensory neurons. Additional experiments demonstrated that short forward pairings of sensory cell activity and restricted applications of the neuromodulatory transmitter serotonin (normally released by the US) differentially enhanced action potential broadening in siphon sensory neurons, relative to backward pairings. Taken together, these results suggest that temporally specific synaptic enhancement engages both spike-width-dependent and spike-width-independent facilitatory processes and that activity-dependent enhancement of presynaptic facilitation may contribute to both the CS-US sequence and proximity requirements of conditioning.

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From Action Potential-Clamp to "Onion-Peeling" Technique – Recording of Ionic Currents Under Physiological Conditions

Patch Clamp Technique ◽

10.5772/35284 ◽

2012 ◽

Cited By ~ 3

Author(s):

Ye Chen-Izu ◽

Leighton T. ◽

Peter P. ◽

Tamas Banyasz

Keyword(s):

Action Potential ◽

Ionic Currents ◽

Physiological Conditions ◽

Action Potential Clamp

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Optimisation of a Generic Ionic Model of Cardiac Myocyte Electrical Activity

Computational and Mathematical Methods in Medicine ◽

10.1155/2013/706195 ◽

2013 ◽

Vol 2013 ◽

pp. 1-20 ◽

Cited By ~ 4

Author(s):

Tianruo Guo ◽

Amr Al Abed ◽

Nigel H. Lovell ◽

Socrates Dokos

Keyword(s):

Action Potential ◽

Time Course ◽

Cardiac Myocyte ◽

Cardiac Tissue ◽

Ionic Currents ◽

Experimental Information ◽

Electrical Stimulus ◽

Right Atrial ◽

Ionic Model ◽

Multiple Datasets

A generic cardiomyocyte ionic model, whose complexity lies between a simple phenomenological formulation and a biophysically detailed ionic membrane current description, is presented. The model provides a user-defined number of ionic currents, employing two-gate Hodgkin-Huxley type kinetics. Its generic nature allows accurate reconstruction of action potential waveforms recorded experimentally from a range of cardiac myocytes. Using a multiobjective optimisation approach, the generic ionic model was optimised to accurately reproduce multiple action potential waveforms recorded from central and peripheral sinoatrial nodes and right atrial and left atrial myocytes from rabbit cardiac tissue preparations, under different electrical stimulus protocols and pharmacological conditions. When fitted simultaneously to multiple datasets, the time course of several physiologically realistic ionic currents could be reconstructed. Model behaviours tend to be well identified when extra experimental information is incorporated into the optimisation.

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