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Lecture Notes andSimulations for Physiology

The notes given below are intended as brief introductions to the simulations contained here. The simulations are Java programs that will run when you click on the items. More detailed theoretical descriptions of the models used in these simulations can be found in the references at the bottom.



The Action Potential

The distinguishing feature of excitable cells like nerves and muscles in vertebrates is their ability to generate the all-or-none electrical event called the action potential. The action potential is elicited when a stimulus exceeding a threshold value is applied to the cell. The properties of the action potential are well described in any standard textbook of physiology. Experimental arrangements for recording the extracellular potential changes can be easily devised in the laboratory. A simple schematic diagram of such an arrangement is shown.

Intracellular recordings are more difficult. An elegant model for explaining the action potential was proposed by Hodgkin and Huxley in the 1950s and is still widely used for instructional purposes.

The Hodgkin-Huxley model of the action potential can be used to understand the role of the sodium and potassium channels, the threshold of excitation for the action potential, refractoriness of the cell membrane to stimulation, etc. See reference 1 (and also reference 2) for more details of the model.

Click on the link below for a simulation of an expanded version of the Hodgkin-Huxley model. Select the stimulation parameters, namely, Pulse Width, Pulse Amplitude, and interpulse Interval from the list boxes. Four traces are plotted in a scrolling display showing 20ms at a time on the screen. The top trace is the stimulus pulse, the second trace is the membrane potential. The bottom two traces are the sodium and potassium conductances (sodium=Green, potassium=Red). Click on the "Pause" button to pause or resume the scrolling animation. The student can change the stimulation parameters at any time and observe the result. [Simulation of the Hodgkin-Huxley model of the Nerve Action Potential]

An important aspect of the nerve action potential is spatial propagation. The depolarization of a small region of membrane will result in a time varying electric field in the neighbourhood which when sufficiently large will cause depolarization of adjacent regions. This will result in spatial propagation. A simulation of this spatio-temporal nature of the action potential is shown here. Click on the link below for the simulation [Simulation of the spatio-temporal propagation of the Action Potential]

Suggested Student Exercises

Using different stimulus parameters determine the combinations that will elicit an action potential. Note than when the interpulse interval is short enough to produce stimuli in the relative refractory period of an action potential, the cell cannot produce an action potential normally but a higher than normal stimulus will elicit an action potential. See if you can determine approximately, the strength-duration curve.

Using the spatio-temporal simulation of the action potential study the propagation velocity of the action potential along the axon.

The Cardiac Vector and the ECG

The depolarization of the myocardium during cardiac activity can be regarded as an effective dipole at any instant resulting from all the cells depolarized at that instant. This is known as the cardiac vector. The ECG is a scalar measurement of the cardiac vector projected on to a lead vector. Most of the normal lead vectors are in one plane. Einthoven who pioneered ECG recording postulated a triangle of three vectors that represented the three primary limb leads of ECG measurement. Subsequently, three additional leads called the augmented vector leads were proposed to observe the cardiac depolarisation at viewing angles intermediate to the primary limb leads. Einthoven's triangle as well as the primary leads and the augmented vector leads are shown in this figure. The primary leads I, II and III are often regarded as forming an equilateral triangle called Einthovens triangle. The augmented vector leads augmented vector left (AVL), augmented vector right (AVR) and augmented vector foot (AVF) are intermediate in angle to the primary limb leads. These six leads and their angles of observation are shown.

The angle of the lead vectors is of primary importance to understand the viewing perspective of the leads. The accompanying figure illustrates how the primary leads and the three augmented leads provide six viewing angles equally dividing the entire plane. The additional six chest leads, not shown here, provide another six viewing perspectives intermediate to these.

During a cardiac cycle the cardiac vector reflects the movement of the depolarization wave from the sino-atrial node, through the atria and then the ventricles, followed by repolarisation of the tissue. The cardiac vector in a single cycle is shown in the adjoining figure. The trace shows the value of the vector (with reference to the origin) at various instants. The axes indicate the horizontal and vertical of the frontal plane. The atrial depolarization is in the upper left quadrant, and ventricular depolarization in the lower right quadrant in the picture (patient right = screen left).

Since, the time varying nature of the cardiac vector is only poorly shown in a static picture a simulation is provided to illustrate time variation. See reference 2 for more details about the cardiac vector and ECG recording.

Click on the link below for a simulation of the cardiac vector from a normal heart. The cardiac vector changes in magnitude and direction during the cardiac cycle, reflecting the depolarization of the atria and ventricles and their subsequent repolarisation. The plot on the left shows the cardiac vector (Blue line) changing with time. The Lead vector is shown as a Red line. The direction of the Lead vector is determined by the position of the lead electrodes. The instantaneous scalar magnitude of the ECG signal is obtained by the projection of the cardiac vector on to the Lead vector line. This projection is shown in Yellow. The right side of the screen shows the ECG trace. The amplitude of the ECG at the vertical axis line is the value of the cardiac vector on to the Lead vector at the present point in time. Select different Lead positions to study the effect of the Lead vector on the same cardiac vector. Click on "Pause" to stop the display. Resume by unclicking "Pause". [Cardiac Vector and ECG simulation]



The Motor Unit Action Potential

The motor unit action potential (MUAP) is the basic electrical activity of muscle in vivo . The recorded motor unit action potential depends not only on the size of the motor unit (i.e., number of muscle fibres), but also the recording arrangement, namely, the electrode dimensions, the inter-electrode spacing and the distance of the electrodes from the motor unit's muscle fibres. The essential difference between intramuscular needle recording and non-invasive surface recording is in the electrode dimensions and distance from the muscle. The MUAP also depends on the end-plate distribution and the action potential propagation velocity. The simulation given here allows you to vary these parameters and understand the importance of each in the MUAP shape. A small motor unit with few muscle fibres (perhaps due to a myopathy) will produce small multiphasic MUAPs whereas a large motor unit resulting from denervation (neuropathy) followed by sprouting of surviving nerve and reinnervation will result in large MUAPs. However, this is only part of the story. The AP propagation velocity and the recording electrode geometry will also influence the shape as can be seen in this simulation. The adjoining figure illustrates the recording electrodes in relation to the muscle fibres of a motor unit. See reference 1 for more details of the model.

Click on the link below to simulate a voluntary EMG with many motor units. Select the different parameters and observe the effect of the recording arrangement as well as the motor unit properties on the recorded MUAP. Note that different motor units with the same number of fibres will not have the same MUAP shape. This can be seen in the simulation by repeating the simulation with the same parameters. The MUAP shape changes since the motor end plate distribution and other geometric features are different. Adjust the amplification suitably (as you would in an EMG machine) to see the MUAP clearly.

[Model of the Motor Unit Action Potential]

For a detailed model of voluntary Electromyogram see the Neuro Science page on this site. [Model of the EMG]



Skeletal Muscle Force Generation

Skeletal muscle force production depends on the muscle fibre type, stimulation rate and the occurence of fatigue. The fibre type determines the speed of contraction (as may be seen in the twitch), and also the fatiguability of the muscle. Muscle fatigue is a complex phenomenon that is still not completely understood. A simple model of skeletal muscle is simulated here to illustrate the phenomena of twitch, summation, tetanic contraction, fatigue and recovery from fatigue. A reasonably accurate model of muscle contraction under normal conditions was developed by A.F.Huxley (1957). The model used in the present simulation is a linearised model that is less accurate but serves the purpose of illustrating basic muscle behaviour. Fatigue being a complex issue, the best functional models of fatigue that are available are empirical ones. A simple pattern of fatigue (fibre type dependent) and recovery is used here. For details about the muscle model see reference 1 below.

Click on the link below to simulate a simple model of skeletal muscle contractile force production. The upper trace in black show the stimuli presented to the muscle, and the lower trace in blue shows the muscle force generated. Select the muscle type and stimulation rate and start stimulation. When stimulation is continued for some time the force slowly drops due to fatigue. If stimulation is stopped the muscle recovers slowly. If the muscle is stimulated for a long time to produce substantial fatigue, the course of recovery can be observed by brief periods of stimulation to see the maximum force production capacity of the muscle. Adjust the amplification to see the twitch more clearly. Use the "Pause" button to stop the display. Note that the muscle type cannot be changed while it is being stimulated; if you try to do that, the simulation is reset. [Model of Skeletal Muscle Force]



References

1. Suresh R. Devasahayam, Signals and Systems in Biomedical Engineering: Signal Processing and Physiological Systems Modeling. Kluwer Academic/ Plenum Publishers, New York, June 2000.

2. R. Plonsey and R.C. Barr, Bioelectricity: A Quantitative Approach, Plenum Press, 1988.

Note: If you have any questions, comments, criticisms on this material please email me: surdev@cmcvellore.ac.in

Suresh Devasahayam