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RBJ 3rd year Neuroscience lecture notes

The alert ones among you will have spotted that Rod MacKinnon has (7th October 2003) won the Nobel Prize for Doyle's 1998 x-ray crystal structure paper...
Doyle, D. A. et al. The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science, 280, 69 - 77, (1998).
You won't be able to download this I daresay, but Rod talks about it here in Nature, as well as in some of the references below. Nature November 2001.
If you are interested, look out for Rod's Nobel acceptance speech when it comes!

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Learning objectives:
Action potential refresher
Voltage Gated Sodium Channel
Voltage Gated Potassium Channel

Links & references available from 29/09/03

Apologies if any of these links are broken, please tell me if they are.  Note that most of these references are not available online, unless you have a subscription, however, the good old library should have them!!  Don't just look at the online ones, they may not be so appropriate.
(I still may pop some more references here later).

Below: Historical, structural theory, diseases, patch clamp and textbooks.

From an historical perspective
Original Hodgkin and Huxley paper, 1952
H & H is an original paper quantifying the action potential, top paper EVER!)

Hodgkin and Huxley at the Royal Society
This paper, in the proceedings of the Royal Society, pretty much reproduces the same information, but it's shorter.

Armstrong, C. M., Bezanilla, F., & Rojas, E. (1973). Destruction of sodium conductance inactivation in squid axons perfused with pronase. J Gen.Physiol 62, 375-391.
Armstrong, C. M. & Bezanilla, F. (1973). Currents related to movement of the gating particles of the sodium channels. Nature 242, 459-461.
A couple of Classics by Clay Armstrong, from the days, prior to serious molecular biology/physiology.

Hille, Armstrong & MacKinnon Ion Channels: From idea to reality, 1999
(H, A and M chat about the role they have played in uncovering the structure and function of ion channels )

Structural theory is presented in:
Francisco Bezanilla The Voltage Sensor in Voltage-Dependent Ion Channels 2000.
(A weighty review discussing the sensor of both sodium and potassium channels.  An excellent source of references).  Also check out his website, it has various models of ion channel function (including sodium and potassium channels).
Prof "Pancho" Bezanilla's Histidine scanning paper is an original article, but skip the maths and it is very accessible:

Dorine M. Starace and Francisco Bezanilla. (2001) Histidine Scanning Mutagenesis of Basic Residues of the S4 Segment of the Shaker K+ Channel. J. Gen. Physiol.117: 469-490.
And reviewed (yet again!!) here (Our subscription had expired last time I looked)
Bezanilla, F. (2002) Perspective: Voltage sensor movements. J. Gen. Physiol. 120:465-473.

The new rival theory of the S4 movements are presented below; You may need to go to the library for them however... (Nature Group Publications are trying to screw the Universities too higher subscription costs I'm afraid).
Structural biology: Life's transistors (non sceptical (!!) Review)
Fred J. Sigworth
Nature
423, 21 - 22 (01 May 2003) News and Views
Full?

X-ray structure of a voltage-dependent K+ channel
Youxing Jiang, Alice Lee, Jiayun Chen, Vanessa Ruta, Martine Cadene, Brian T. Chait, Roderick MacKinnon
Nature
423, 33 - 41 (01 May 2003) Article
Abstract, Full?

The principle of gating charge movement in a voltage-dependent K+ channel
Youxing Jiang, Vanessa Ruta, Jiayun Chen, Alice Lee, Roderick MacKinnon
Nature
423, 42 - 48 (01 May 2003) Article
Abstract, Full?

Discussion or activation, inactivation coupling is found in many places, including:
John C. Rogers, Yusheng Qu, Timothy N. Tanada, Todd Scheuer, and William A. Catterall. Molecular Determinants of High Affinity Binding of alpha -Scorpion Toxin and Sea Anemone Toxin in the S3-S4 Extracellular Loop in Domain IV of the Na+ Channel alpha Subunit. J.Biol.Chem. 271 (27):15950-15962, 1996.

Also, good are the following, particularly Catterall!
R. W. Aldrich. Fifty years of inactivation. Nature 411 (6838):643-644, 2001.
W. A. Catterall. Structure and function of voltage-gated ion channels. Trends Neurosci. 16 (12):500-506, 1993.
W. A. Catterall. From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels. Neuron 26 (1):13-25, 2000.
A. L. Goldin. Resurgence of sodium channel research. Annu.Rev.Physiol 63:871-894, 2001.

You may find discussion of several hereditary diseases involving ion channel mutations useful:
F. Lehmann-Horn and K. Jurkat-Rott. Voltage-gated ion channels and hereditary disease. Physiol Rev. 79 (4):1317-1372, 1999.
But note this review does not include any discussion of the very important autoimmune related disorders.

On the subject of patch clamp
Several standard textbooks contains details, else more interesting is the Scientific American article:
E. Neher and B. Sakmann. The patch clamp technique. Sci.Am 266 (3):44-51, 1992.

The papers written by Sakmann and Neher on receipt of their Nobel prizes contain some detail and are available here:
Sakmann.
Neher.
These guys also have a website showing Quick time videos of patching here.
A couple of the original patch clamp papers are:
("Single Channel") Neher, E. & Sakmann, B. (1976). Single-channel currents recorded from membrane of denervated frog muscle fibres. Nature 260, 799-802.

("Whole-cell") O. P. Hamill, A. Marty, E. Neher, B. Sakmann, and F. J. Sigworth. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 391 (2):85-100, 1981.

Textbooks
Ionic Channels of Excitable Membranes
B. Hille.  Either first or second editions are OK.

Also, very good, and may be, more accessible is:
Ion Channels: Moleculse in Action
D.J.Aidley & P.R.Stanfield, 1996, Cambridge University Press
ISBN 0 521 49531 8 (HBA), or ISBN 0521 49882 1 (PBK).

Notes; Some of these papers require the FREE Adobe Acrobat Reader   to be installed on your computer.  They can mostly be read using a Brum University computer (they are "IP authorised" sites).

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