Systems Neuroscience Introduction to Ion Channels

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Systems NeuroscienceIntroduction to Ion Channels

• 8/31/2005

Vladimir Brezina Dept. of Neuroscience, Mt.
Sinai Annenberg 21-220 x46532 Vladimir.Brezina_at_mss
m.edu
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Introduction to Ion Channels

• Macroscopic ion currentsmicroscopic ion channels
• Patch-clamp recording techniques
• Ion channels as membrane transport proteins
• Ion-channel classes and general structure
• Analysis of single-channel records
• Superfamily of voltage-gated Na, K, and Ca
  channels ion permeation and gating
• Ion-current functions in neuronal signaling

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Introduction to Ion Channels

• Macroscopic ion currentsmicroscopic ion channels

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From Hille B (2001) Ion Channels of Excitable
Membranes (3rd ed). Sinauer, Sunderland, MA.
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1 pA
1 nA
Modified from Levitan IB, Kaczmarek LK (1991) The
Neuron Cell and Molecular Biology. Oxford
University Press, New York.
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Introduction to Ion Channels

• Macroscopic ion currentsmicroscopic ion channels
• Patch-clamp recording techniques

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From Stühmer W, Roberts WM, Almers W (1983) The
loose patch clamp, in Single-Channel Recording,
Sakmann B, Neher E, eds. Plenum, New York.
From Kandel ER, Schwartz JH, Jessell TM, eds
(2000) Principles of Neural Science (4th ed).
McGraw-Hill, New York.
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(No Transcript)
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(cell-attached)
Modified from Corey DC (1983) Patch
clamp current excitement in membrane
physiology. Neurosci Comment 1 99-110.
Know and manipulate ionic and
chemical voltage composition -------------
--------------------------- outside only outside
only both both, inside easy both both,
outside easy both both, outside easy
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Introduction to Ion Channels

• Macroscopic ion currentsmicroscopic ion channels
• Patch-clamp recording techniques
• Ion channels as membrane transport proteins

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The problem
A ubiquitous solution
From Hille B (2001) Ion Channels of Excitable
Membranes (3rd ed). Sinauer, Sunderland, MA.
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Figure 8.14 Schematic diagram of different types
of membrane transport mechanisms.
Modified from Weiss TF (1996) Cellular
Biophysics, Volume 1 Transport. MIT Press,
Cambridge, MA.
Figure 6.4 Schematic diagram of a hypothetical
carrier mechanism.
Channel
Carrier
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Introduction to Ion Channels

• Macroscopic ion currentsmicroscopic ion channels
• Patch-clamp recording techniques
• Ion channels as membrane transport proteins
• Ion-channel classes and general structure

16
From Hille B (2001) Ion Channels of Excitable
Membranes (3rd ed). Sinauer, Sunderland, MA.
17
From Kandel ER, Schwartz JH, Jessell TM, eds
(2000) Principles of Neural Science (4th ed).
McGraw-Hill, New York.
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From Johnston D, Wu SM-S (1995) Foundations of
Cellular Neurophysiology. MIT Press, Cambridge,
MA.
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From Hille B (2001) Ion Channels of Excitable
Membranes (3rd ed). Sinauer, Sunderland, MA.
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From Kandel ER, Schwartz JH, Jessell TM,eds
(2000) Principles of Neural Science (4th ed).
McGraw-Hill, New York.
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Introduction to Ion Channels

• Macroscopic ion currentsmicroscopic ion channels
• Patch-clamp recording techniques
• Ion channels as membrane transport proteins
• Ion-channel classes and general structure
• Analysis of single-channel records

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Analysis

• Preliminaries
• Which is the baseline and which the open-channel
  current?
• How many channels?
• Permeation (open-channel characteristics)
• Gating (transitions between open and closed
  states)

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Modified from Kandel ER, Schwartz JH, Jessell
TM, eds (2000) Principles of Neural Science (4th
ed). McGraw-Hill, New York.
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inward rectification
outward rectification
Modified from Kandel ER, Schwartz JH, Jessell
TM, eds (2000) Principles of Neural Science (4th
ed). McGraw-Hill, New York.
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From Hille B (2001) Ion Channels of Excitable
Membranes (3rd ed). Sinauer, Sunderland, MA.
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From Johnston D, Wu SM-S (1995) Foundations of
Cellular Neurophysiology. MIT Press, Cambridge,
MA.
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b
C
O
a
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From Ogden D, Stanfield P (1987) Patch clamp
techniques for single channel and whole-cell
recording, and Colquhoun D, Hawkes AG (1987) The
interpretation of single channel recordings, in
Microelectrode Techniques, Ogden D, ed. Company
of Biologists, Cambridge.
From Johnston D, Wu SM-S (1995) Foundations of
Cellular Neurophysiology. MIT Press, Cambridge,
MA.
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depolarize
hyperpolarize
From Catterall WA (1988) Structure and function
of voltage-sensitive ion channels. Science 242
50-61.
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Introduction to Ion Channels

• Macroscopic ion currentsmicroscopic ion channels
• Patch-clamp recording techniques
• Ion channels as membrane transport proteins
• Ion-channel classes and general structure
• Analysis of single-channel records
• Superfamily of voltage-gated Na, K, and Ca
  channels ion permeation and gating

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(No Transcript)
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From Kandel ER, Schwartz JH, Jessell TM, eds
(2000) Principles of Neural Science (4th
ed). McGraw-Hill, New York.
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Which part of the structure forms the channel
pore and the selectivity filter?
From Catterall WA (1988) Structure and
function of voltage-sensitive ion channels.
Science 242 50-61.
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From Stevens CF (1991) Making a submicroscopic
hole in one. Nature 349 657-658.
36
From Hille B (2001) Ion Channels of Excitable
Membranes (3rd ed). Sinauer, Sunderland, MA.
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Modified from Zhou Y, Morais-Cabral JH, Kaufman
A, MacKinnon R (2001) Chemistry of ion
coordination and hydration revealed by a
K channel-Fab complex at 2.0 Å resolution.
Nature 414 43-48.
From Aidley DJ, Stanfield PR (1996) Ion
Channels. Cambridge University Press, Cambridge.
Figure 2 View of electron density in the region
of the K channel selectivity filter. The
2Fo - Fc electron density map (contoured at 2 )
covers amino acids forming the selectivity filter
(two diagonally opposed subunits are shown), with
K ions (green spheres) along the ion pathway,
and water molecules (red spheres) in the
vicinity.
Figure 5 High- and low-K structures of the
selectivity filter. a, The high-K structure with
K ions (green spheres) in filter positions 14
(top to bottom). Each K ion is located at the
centre of eight oxygen atoms. The distances
between the K ions and the oxygen atoms (black
dashed lines) above/below are position 1,
2.80/3.08 Å position 2, 2.72/2.83 Å position 3,
2.85/2.70 Å position 4, 2.94/2.88 Å. Important
hydrogen bonds (blue dashed lines) and a buried
water molecule (red sphere) are shown. For
clarity, the subunit closest to the viewer has
been removed and side chains of the following
residues are not shown Thr 72, Ala 73, Thr 74
and Leu 81 of all three subunits, and Val 76 and
Tyr 78 from the subunit at the back. b, The
low-K structure. Atoms are represented as in a.
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Which part of the structure senses membrane
voltage and mediates voltage-dependent activation?
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From Baldwin TJ, Isacoff E, Li M, Lopez GA, Sheng
M, Tsaur ML, Jan YN, Jan LY (1992) Elucidation
of biophysical and biological properties of
voltage-gated potassium channels. Cold Spring
Harbor Symp Quant Biol 57 491-499.
From Hille B (2001) Ion Channels of
Excitable Membranes (3rd ed). Sinauer,
Sunderland, MA.
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From Hille B (2001) Ion Channels of
Excitable Membranes (3rd ed). Sinauer,
Sunderland, MA.
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Which part of the structure mediates fast
inactivation?
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From Hille B (2001) Ion Channels of
Excitable Membranes (3rd ed). Sinauer,
Sunderland, MA.
43
From Hille B (2001) Ion Channels of
Excitable Membranes (3rd ed). Sinauer,
Sunderland, MA.
44
Introduction to Ion Channels

• Macroscopic ion currentsmicroscopic ion channels
• Patch-clamp recording techniques
• Ion channels as membrane transport proteins
• Ion-channel classes and general structure
• Analysis of single-channel records
• Superfamily of voltage-gated Na, K, and Ca
  channels ion permeation and gating
• Ion-current functions in neuronal signaling

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From Zigmond MJ, Bloom FE, Landis SC, Roberts JL,
Squire LR, eds (1999) Fundamental
Neuroscience. Academic Press, San Diego.
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From Zigmond MJ, Bloom FE, Landis SC, Roberts JL,
Squire LR, eds (1999) Fundamental
Neuroscience. Academic Press, San Diego.
47
From Hille B (2001) Ion Channels of
Excitable Membranes (3rd ed). Sinauer,
Sunderland, MA.
48
From Hille B (2001) Ion Channels of
Excitable Membranes (3rd ed). Sinauer,
Sunderland, MA.
From Rogawski MA (1985) The A-current how
ubiquitous a feature of excitable cells is
it? Trends Neurosci 8 214-219.
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IK
Modified from Hille B (2001) Ion Channels of
Excitable Membranes (3rd ed). Sinauer,
Sunderland, MA.
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From Gorman ALF, Hermann A, Thomas MV
(1981) Intracellular calcium and the control
of neuronal pacemaker activity. Fed Proc 40
2233-2239.
From Hille B (2001) Ion Channels of Excitable
Membranes (3rd ed). Sinauer, Sunderland, MA.
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From Hille B (2001) Ion Channels of
Excitable Membranes (3rd ed). Sinauer,
Sunderland, MA.
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From Hille B (2001) Ion Channels of
Excitable Membranes (3rd ed). Sinauer,
Sunderland, MA.
Ca channel
other channels

?V
messenger Ca2
other processes
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From Fox AP, Nowycky MC, Tsien RW (1987) Kinetic
and pharmacological properties distinguishing
three types of calcium currents in chick
sensory neurones. J Physiol (Lond) 394 149-172.
From Hille B (2001) Ion Channels of
Excitable Membranes (3rd ed). Sinauer,
Sunderland, MA.
54
From Hille B (2001) Ion Channels of
Excitable Membranes (3rd ed). Sinauer,
Sunderland, MA.
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From Hongo K, Tanaka E, Kurihara S (1993)
Alterations in contractile properties and Ca2
transients by ß- and muscarinic receptor
stimulation in ferret myocardium. J Physiol
(Lond) 461 167-184.
From Hille B (2001) Ion Channels of
Excitable Membranes (3rd ed). Sinauer,
Sunderland, MA.
From Fischmeister R, Hartzell HC (1986)
Mechanism of action of acetylcholine on calcium
current in single cells from frog ventricle. J
Physiol (Lond) 376 183-202.