Hodgkin and Huxley (1952) PDF

Hodgkin and Huxley (1952) Prof. Varadhan SKM Department of Applied Mechanics and Biomedical Engineering Creator: Prosser, C. Ladd (Clifford Ladd), 1907-; Bishop, David W Website, https://www.flickr.com/photos/internetarchivebookimages/20047497644 Public domain In this class… 1. Theory befo...

Hodgkin and Huxley (1952) Prof. Varadhan SKM Department of Applied Mechanics and Biomedical Engineering Creator: Prosser, C. Ladd (Clifford Ladd), 1907-; Bishop, David W Website, https://www.flickr.com/photos/internetarchivebookimages/20047497644 Public domain In this class… 1. Theory before Hodgkin and Huxley 2. A series of five papers 3. Paper 1 4. Paper 2 5. Paper 3 6. Paper 4 7. Paper 5  Theory before Hodgkin and Huxley Van’t Hoff theory of osmosis on solutions (1887), hypothesis of dissociation of salts into ions by Arrhenius (1887), and dilution law by Ostwald (1888) Nernst’s equation (1897): 𝑉=𝑅𝑇/𝐹 𝑙𝑜𝑔⁡〖 [𝐶]_1/[𝐶]_2 〗 where R is the gas constant, T is the absolute temperature, and F is the Faraday constant. The brackets indicate the concentrations of ion C on each side of the cell. Bernstein hypothesis (1902): Bernstein’s membrane theory Modern era of experimental neurophysiology (1930s)  A series of five papers Experimental method, behavior of the membrane in a normal ionic environment. Effect of changes in sodium concentration, resolution of the ionic current into sodium and potassium currents. Permeability - in units of ionic conductance. Effect of sudden changes in potential on the time course of the ionic conductances Inactivation process which reduces sodium permeability during the falling phase of the spike. Concludes the series and shows that the form and velocity of the action potential may be calculated from the results described  Paper 1 Paper 1: Measurement Of Current-voltage Relations In The Membrane Of The Giant Axon Of Loligo Aim: Experimental method, behavior of the membrane in a normal ionic environment Experimental set-up: Two silver-wire internal electrode, guard system to measure membrane current, feed-back amplifier for clamping the voltage at any desired level Result: 1. All-or-nothing action potential – 100mV when stimulated with a brief shock 2. 15mV Threshold 3. Graded responses at 10-15 mV 4. Depolarization < 15 mV  outward currents 5. Depolarization = 15 mV – 110 mV  initially inward current, then outward Creator: Museum of Veterinary Anatomy FMVZ USP, https://commons.wikimedia.org/wiki/File:Squid_%E2%80%9CLoligo_sp.%E2%80%9D.jpg CC-BY-SA 4.0 The membrane potential is measured Current through the open channel = (-1) * current passed by the voltage clamp Compared with the desired value Voltage No error == exists Yes Current is passed to drive the membrane potential to the desired potential Ion Voltage clamp Yes No channel == open Creator: smonsays, https://commons.wikimedia.org/wiki/File:Voltage_clamp_setup.svg CC-BY-SA 4.0  Depolarization = 110 mV  inward current disappeared, replaced by one of outward current 6. Relation b/n ionic current and membrane potential. This relation = rising phase of the action potential 7. Maximum inward and outward ionic current – temperature-sensitive. Rate of change – increased threefold for a rise of 10 deg C 8. Compensated feedback reduced error due to the resistance by membrane capacitance mV Sample waveform obtained due to sodium current Modified from: Hodgkin Huxley 1952  Paper 2 Paper 2: CURRENTS CARRIED BY SODIUM AND POTASSIUM IONS THROUGH THE MEMBRANE OF THE GIANT AXON OF LOLIGO Aim: Effect of changes in sodium concentration, resolution of the ionic current into sodium and potassium currents Inward currents = sodium ions Inward current  rising phase of action potential (concentration and potential differences) Choline – inert cation used (no decrease in resting potential) Isotonic Choline sea water (33  9 gm/L), sea water Result: 1. The initial inward current for 10 – 100 mV depolarization was reversed when replacement with Choline happened 2. Depolarization  increase in membrane permeability for sodium ion in either direction 3. Simple assumptions – Total ionic current = Sodium current + Potassium current 4. Time course of permeability 5. Sodium conductance – increases rapidly, declines = approximately exponential curve Potassium conductance – S-shaped curve, held at maximum for a longer time 6. At depolarization of 100 mV the conductances = 30 m.mho/ 7. Ions cross the membrane independently of one another Conductance curves of Sodium (left) and Potassium (right) Modified from: Hodgkin Huxley 1952a  Paper 3 Paper 3: THE COMPONENTS OF MEMBRANE CONDUCTANCE IN THE GIANT AXON OF LOLIGO Aim: Effect of sudden changes in potential on the time course of the ionic conductances Discontinuities in the sodium current can be observed when the depolarization time is cut-short by exploiting the membrane potential When sodium is substituted with Choline even the repolarization tail of the potential curve vanishes This experiment was made possible by changing the pulse given to the feed-back amplifier The corresponding mV curves when the pulse input to the feedback amplifier was varied Modified from: Hodgkin Huxley 1952b A. In sea water (110 mV, 0.28 msec) B. In choline sea water Modified from: Hodgkin Huxley 1952b  Paper 4 Paper 4: THE DUAL EFFECT OF MEMBRANE POTENTIAL ON SODIUM CONDUCTANCE IN THE GIANT AXON OF LOLIGO Aim: Inactivation process which reduces sodium permeability during the falling phase of the spike Gap in the previous experiments - no information about the rate at which repolarization restores the ability of the membrane to respond with its characteristic increase of sodium conductance It deals with the 'inactivation' process Quantitative evidence about the influence of membrane potential on the process responsible for inactivation Similar to the previous paper two pulses were given and the results were observed The early effects are a rapid increase in sodium conductance when the fiber is depolarized and a rapid decrease when it is repolarized. The late effects are a slow onset of a refractory or inactive condition during a maintained depolarization and a slow recovery following repolarization  Paper 5 Paper 5: A QUANTITATIVE DESCRIPTION OF MEMBRANE CURRENT AND ITS APPLICATION TO CONDUCTION AND EXCITATION IN NERVE Aim: Concludes the series and shows that the form and velocity of the action potential may be calculated from the results described previously This paper discusses the results of preceding papers, puts them into mathematical form, showed that this accounts for conduction and excitation in quantitative terms Three types of channels: Sodium, Potassium, and leakage channels. The individual gates open and close randomly and quite rapidly, but the probability of a gate being open (the open probability) is dependent on the voltage across the membrane. Major conclusion - the responses of an isolated giant axon of Loligo to electrical stimuli are due to reversible alterations in sodium and potassium permeability arising from changes in membrane potential. Good agreement was obtained in the following cases: (a) The form, amplitude and threshold of an action potential under zero membrane current at two temperatures. (b) The form, amplitude and velocity of a propagated action potential. (c) The form and amplitude of the impedance changes associated with an action potential. (d) The total inward movement of sodium ions and the total outward movement of potassium ions associated with an impulse. (e) The threshold and response during the refractory period. (f) The existence and form of subthreshold responses. Electrical circuit representing the membrane (g) The existence and form of an anode break response. (h) The properties of the subthreshold oscillations seen in cephalopod axons. The theory also predicts that a direct current will not excite if it rises sufficiently slowly The calculated exchange of potassium ions is Modified from: Hodgkin Huxley 1952d Modified from: Hodgkin Huxley 1952d  Simplest equation, independent of the magnitude or sign of V, little affected by the time course of V Takes no account of the dielectric loss in the membrane. No simple way of estimating the error introduced by this approximation I often say to young people if you discover something and don’t put it into context and don’t pursue it to the point where you can put it in the context, it will be lost - Andrew Huxley in an interview. References 1. Hodgkin AL, Huxley AF (1952a) Currents carried by sodium and potassium ions through the membrane of the giant axon of Loligo. J Physiol 116:449 – 472. Medline 2. Hodgkin AL, Huxley AF (1952b) The components of membrane conductance in the giant axon of Loligo. J Physiol 116:473–496. Medline 3. Hodgkin AL, Huxley AF (1952c) The dual effect of membrane potential on sodium conductance in the giant axon of Loligo. J Physiol 116:497–506. Medline 4. Hodgkin AL, Huxley AF (1952d) A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol 117:500 –544. Medline 5. Hodgkin AL, Huxley AF, Katz B (1952) Measurement of current-voltage relations in the membrane of the giant axon of Loligo. J Physiol 116:424 – 448. Medline 6. Neuromethods, Vol. 14. Neurophysiological Technrques: Basic Methods and Concepts Edlted by: A. A Boulton, G B. Baker, and C. H Vandetwolf Copyright Q 1990 The Humana Press Inc , Clifton, NJ Summary 1. Theory before Hodgkin and Huxley 2. A series of five papers 3. Paper 1 4. Paper 2 5. Paper 3 6. Paper 4 7. Paper 5