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last modified 19 January 2006
Neurobiology Lectures:
Electrical Properties of Cells 1. Resting Potential and 2. Action Potential
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ELECTRICAL PROPERTIES OF CELLS - INDEX
1. Course Introduction: Molecules, cells, circuits and the phylogeny of animals.
2. Resting Potential Ion gradients, Membrane voltages, Nernst and Goldman Equations ("no current no volts")
3. Action Potential
AP1: Squids, Hodgkin & Huxley, Voltage Clamp & Ion Currnts
AP2: Voltage Sensitive Ion Channels; Cloning the Na+ and K+ channels
AP3: Single Ion Channels: Patch Clamp and Mutagenic Analysis
AP4: Ionic Currents and the Propogation of Action Potentials.
AP Papers
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Introductory Lecture
Introductory Slides (HTML File): History and Neurons
Game of Life: surprising order can emerge from simple rules.
Bibliography of Cognative Behavior (The Cognative Animal ? MIT Press ? ISBN 0-262-02514-0 (2002))
Tree of Life an academically reputable view of phylogeny
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Resting Potential Lectures
RP and AP Papers
Nernst Potential / Goldman Equation Handout and PROBLEM SET
Nernst Potential / Goldman Equation Work sheet (Excel Spread Sheet)
Description of the constant units of Nernst/Goldman Equations (Excel Spread Sheet)
PAPER: Young (1936) Description of Squid Giant Axon
PAPER: Hodgkin & Huxley (1939) First Action Potential Recording
PAPER: Hodgkin & Huxley (1945)
Further details of their 1939 study.
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Action Potential Lectures: 4 Parts
RP and AP Papers
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RP and AP Papers
The Action Potential 1: Hodgkin & Huxley and the Squid Giant Axon & "Whole Cell" Voltage Clamp.
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RP and AP Papers
The Action Potential 2: Voltage Sensitive Ion Channels; Cloning the Na+ and K+ channels.
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RP and AP Papers
The Action Potential 3 (outline): Neher and Sakman and Analysis of Single Ion Channels (Patch Clam), and Mutagenic Analysis of Ion Channel Properties
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RP and AP Papers
The Action Potential 4: Ionic Currents and the Propogation of Action Potentials.
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Resting Potential / Action Potential References
Background Papers: Young, Goldman & Keynes
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Young JZ (1936) The structure of nerve fibres in cephalopods and crustacea. Proc. Roy. Soc. Lond. B. 121, 319-337.
[Discription of giant axon of squid Loligo forbesi.]
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Goldman DE (1943) Potential, impedance, and rectification in membranes. Journal of General Physiology 27, 37-60.
[Origin of the Goldman Equation.]
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Keynes RD (1951) The ionic movements during nervous activity. Journal of Physiology 114, 119-150.
[Source of permeability values in Goldman Equation. ]
- PDF
Keynes RD, Lewis PR (1951) The sodium and potassium content of cephalopod nerve fibres. Journal of Physiology 114, 151-182.
The Action Potential: Na+ and K+ currents: Hodgkin, Huxley, Katz and Hille.
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Hodgkin AL & AF Huxley (1939) Action potentials recorded from inside a nerve fibre. Nature 144, 710-711.
[First published record of action potential measured with intracellular electrode.]
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Hodgkin AL, Huxley AF (1945) Resting and action potentials in single nerve fibres. Journal of Physiology 104, 176-195.
[Further details of 1939 study.]
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Hodgkin AL, Huxley AF (1949) The effect of of sodium ions on the electrical activity of the giant axon of the squid. Journal of Physiology 108, 37-77.
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Hodgkin AL, Huxley AF (1949) The effect of temperature on the electrical activity of the giant axon of the squid. Journal of Physiology 109, 240-249.
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Huxley AF, Stampfli R (1949) Evidence for saltatory conduction in peripheral myelinated nerve fibres. Journal of Physiology 108, 315-339.
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Hodgkin AL, Huxley AF, Katz B (1952a) Measurement of current-voltage relations in the membrane of the giant axon of Loligo. Journal of Physiology 116, 424-448.
[Major Voltage Clamp study of ion currents during AP.]
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Hodgkin AL, Huxley AF (1952b) Currents carried by sodium an potassium ions through the membrane of the giant axon of Loligo. Journal of Physiology 116, 449-472.
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Hodgkin AL, Huxley AF (1952c) The components of membrane conductance in the giant axon of Loligo. Journal of Physiology 116, 473-496.
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Hodgkin AL, Huxley AF (1952d) The dual effect of membrane potential on sodium conductance in the giant axon of Loligo. Journal of Physiology 116, 497-506.
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Hille B (1970) Ionic channels in nerve membranes. Progress in Biophysics and Molecular Biology 21, 1-32.
[Use of TEA and TTX to verify Na+ and K+ currents in AP.]
Cloning and Characterizing Voltage Sensitive Ion Channels (Na+ & K+)
- PDF Catterall WA (1984) The molecular basis of neruonal excitability. Science 223, 653-661. [State of knowledge of Na+ channel year onw was cloned.]
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Noda M, S Shimizu, T Tanabe, T Takai, T Kayano, T Ikeda, H Takahashi, H Nakayama, Y Kanaoka, N Minamino, K Kangawa, H Matsuo, MA Raftery, T Hirose, S Inayama, H Hayashida, T Miyata & S Numa (1984) Primary structure of Electrophorus electricus sodium channel deduced from cDNA sequence. Nature 312, 121-127. [Cloning of a Na+ channel.]
- Kaplan WD & WE Trout (1969) The behavior of four neurological mutants of Drosophila. Genetics 61, 399-409.
[Identification of the Shaker mutant.]
- Trout WE & WD Kaplan (1973) Genetic manipulations of motor output in Shaker mutants of Drosophila. Journal of Neurobiology 4, 495-512.
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Slakoff L & R Wyman (1981) Outward currents in developing Drosophila flight muscle. Science 212, 461-463.
[Differential expression of K-DR and K-A currents in developing flight muscle.]
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Salkoff L & R Wyman (1981) Genetic modification of potassium channels in Drosophila Shaker mutants. Nature 293, 228-230.
[Identification that Shaker is a K-A channel mutant.]
- Salkoff LB & RJ Wyman (1983) Ion currents in Drosophila flight muscles. Journal of Physiology 337, 687-709.
- Schwarz TL, BL Tempel, DM Papazian, YN Jan & LY Jan (1988a) Multiple potassium channel components are produced by alternative splicing at the Shaker locus in Drosophila. Nature 331, 137-142. [Cloning of a Shaker K+ channel.]
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Timpe LC, TL Schwarz, BL Tempel, DM Papazian, Y Nung & LY Jan (1988b) Expression of functional potassium channels from Shaker cDNA in Xenopus oocytes. Nature 331, 143-145.
[Express and compare currents of two expressed alt. spliced clones.]
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MacKinnon R (2003) Potassium channels (minireview). FEBS Letters 555, 62-65.
[3D structure of K+ channel.]
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Bichet D, Haass FA, Jan LY (2003) Merging functional studies with structures of inward-rectifier K+ channels. Nature Reviews Neuroscience 4, 957-967. [ function ? 3D structure K+ channels]
- ABSTRACT
Jentsch TJ & Gunther W (1997) Chloride channels: an emerging molecular picture. BioEssays 19, 117-126.
[Review of voltage sensitive Cl- channels.]
Na+ Channel Diversity
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Lopreato GF, Lu Y, Southwell A, Atkinson NS, Hillis DM, Wilcox TP, Zakon HH (2001) Evolution and divergence of sodium channel genes in vertebrates. Proceedings of the National Academy of Sciences, USA 98, 7588-7592.
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Catterall WA, Goldin AL, Waxman SG (2003)Compendium of voltage-gated ion channels: Sodium Channels. Pharmacological Reviews 55, 575-578.
K+ Channel Diversity
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Jan LY & Jan YN. (1997) Cloned potassium channels from eukaryotes and prokaryotes. Annual Review of Neuroscience 20, 91-123. [ includes K+ leakage channels Kir]
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Grigoriev NG, Spafford JD, Gallin WJ, Spencer AN. (1997) Voltage sensing in jellyfish Shaker K+ channels. Journal of Experimental Biology 200, 2919-2926.
[K+ channels in jellyfish]
- Schwarz TL, BL Tempel, DM Papazian, YN Jan & LY Jan (1988) Multiple potassium-channel components are produced by alternative splicing at the Shaker locus in Drosophila. Nature 331, 137-142.
[K+ channel genes alternatively spliced in flies, less so in vertebrates]
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Salkoff L, K Baker, A Butler, M Covarrumias, MD Pak & A Wei (1992) An essential 'set' of K+ channels conserved in flies, mice and humans. Trends in Neuroscience 15, 161-166.
[Comparison of genes between divergent animals]
- Pongs O (1992) Structural basis of voltage-gated K+ channel pharmacology. Trends in Pharmacological Sciences 13, 359-365.
- Wei A, Jegla T, Salkoff L (1996) Eight potassium channel families evealed by the C. elegans genome project. Neurophamacology 35, 805-829.
[K+ channel gene family in a divergent phylum (basal protostome)]
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Stansfeld C, Ludwig J, Roeper J, Weseloh R, Brown D, Pongs O (1997) A physiological role for either-a-go-go K+ channels? Trends in Neuroscience 20, 13-14.
[ M-current channels ? modulating thresholds]
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Miller C (2000) An overview of the potassium channel family. Genome Biology 1(4):reviews0004.1?0004.5
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Brown BS, Yu SP (2000) Modulation and genetic identification of the M channel. Progress in Biophysics and Molecular Biology 73, 135-166.
[ M-current channels ? modulating thresholds]
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Minor Jr. DL (2001) Potassium channels: life in the post-structural world. Current Opinion in Stuctural Biology 11, 408-414.
[ 3D K+ channel structure]
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Bichet D, Haass FA, Jan LY (2003) Merging functional studies with structures of inward-rectifier K+ channels. Nature Reviews Neuroscience 4, 957-967. [ function - 3D structure K+ channel]
- PDF
McCormack TJ (2003) Comparison of K+ channel genes within the genomes of Anopheles gambiae and Drosophila melanogaster. Genome Biology 4, R58
[K+ channel divergence between two closely related species: fly and mosquito (both Diptera)]
Case Studies: Biophysical and Molecular Biological Studies of Ion Channels (and an odorant receptor) ? Methodologies.
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Neher E & B Sakmann (1976) Single-channel currents recorded from membrane of denervated frog muscle fibres. Nature 260, 799-802.
[Development of Patch Clamp technique ? recording single ion channel events]
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Hoshi T, WN Zagotta & RW Aldrich (1990) Biophysical and molecular mechanisms of Shaker potassium channel inactivation. Science 250, 533-538.
[PART 1: Mutagenic analysis of inactivation mechanism ? single chanels and frog oocytes]
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Zagotta WN, T Hoshi & RW Aldrich (1990) Restoration of inactivation in mutants of Shaker potassium channels by a peptide derived from ShB. Science 250, 568-571.
[PART 2: Mutagenic analysis of inactivation mechanism ? single chanels and frog oocytes]
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Hartmann HA, GE Kirsch, JA Drewe, M Taglialatela, RH Joho, AM Brown (1991) Exchange of conduction pathways between two related K+ channels. Science 251, 942-944.
[Mutagenic/chimeric study of TEA binding site in K+ channel]
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Hallem EA, Fox AN, Zweiebel LJ, Carlson JR (2004) Mostuito receptor for human-sweat odorant. Nature 427, 212-213.
[Expressing neuronal gene in alternative species to test function]
Reviews of Biophysics Ion Channels
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Hille B (1970) Ionic channels in nerve membranes. Progress in Biophysics and Molecular Biology 21, 1-32.
[Review of ion channels circa 1970 - insightful]
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Neher E (1992) Ion channels for communication between and within cells. Neuron 8, 605.
[Nobel Prize Lecture]
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Sakmann B (1992) Elementary steps in synaptic transmission refvealed by current through single ion channels. Neuron 8, 613.
[Nobel Prize Lecture]
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Goldin AL (2003) Mechanisms of sodium channel inactivation. Current Opinion in Neurobiology 13, 284-290.
Modeling Ionic Currents, Propogation of Action Potentials
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Segev I (1992) Single neuron models: oversimple, complex and reduced. Trends in Neuroscience 15, 414-421.
[Computational Neuroscience ? modeling dendrites and axons]
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