Ion Channels and Pumps
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Transcript of Ion Channels and Pumps
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0.3 pA
0.6 pA
-0.3 pA
pA = 10-12A
-0.6 pA
+30 mV
-30 mV
-60 mV
0 mV
+60 mV
Similar to quiz
problem
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Ion Channels and Pumps
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top view
Example: one of many types of K+ channel
side view
25 250 K Dalton
protein complexes
Coil up, insert into
membrane
Consist of multiplesubunits (same or
different)
Each subunit consists of
several membrane-
spanning regions
Channel forms a water-filled pore through which
ions flow passively (i.e.
not requiring energy)
What is an ion channel
physically?
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Ion channels are composed of
several subunits
Note about physical distribution of channels in a cells plasma membrane:
A 10 um diameter cell is like a basketball made out of office paper
Example: voltage-dependent Na+ channels occur at density of ~2/um^2
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Each subunit has multiple
membrane-spanning regions
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Are ion channels
selective?
Some no (as in certain
bacterial toxins)
Most are highly selective
Important ones in the brain:
Na+, K+, Cl-, Ca++, +mixed Despite selectivity, they may
conduct up to 100 million
ions per second
Selectivity can be
mediated:
by size
by molecular sieve
Most ion channels are highly selective
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Ion channels can be gated in multiple ways
Gating can
occur: by voltage
mechanically
by chemical ligand
(outside the cell) by phosphorylation
(inside the cell)
or not gated at all
Gating involves:
A local conformational
change
or a global structural
change
or a gating particle
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Channels can be modeled as linear resistors
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But truth be told, ion channels are not reallylinear,
but in this class we pretend.
Acts like higherconductance whenflowing from high[C] to low [C]
Determining K+ channel activation curves from K+ channel currents often requires the Goldman-Hodgkin-Katz equation
John R. Clay *http://www.frontiersin.org/cellularneuroscience/paper/10.3389/neuro.03/020.2009/
http://www.frontiersin.org/cellularneuroscience/paper/10.3389/neuro.03/020.2009/http://www.frontiersin.org/cellularneuroscience/paper/10.3389/neuro.03/020.2009/ -
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Note: channels are generally either open or closed, but the
open probability can vary continuously, so at a population
level, ionic conductances look continuous
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By contrast, a pump burns ATP
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Ion Selectivity Is Based On Dehydration Energy
Profiles
K+
H
OH
Na+
H
OH
K+Na+
hydrated Na+ orhydrated K+ orKcsA-hydrated K+
KcsA-hydrated Na+
DG = 5-10 kcal/mol
Selectivity filters of channel subunits
Ionic radius of K+: 1.33 Ionic radius of Na+: 0.95
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Potassium Ions Are Transported In The Dehydrated Form
Zhou et al. (2001)
Crystal structures contain two K+ ions separated by a water molecule, either as K-water-K-water, or as water-K-water-K.
High throughput is due to destabilization of the ion-protein binding by mutual repulsion between a bound ion and an
approaching ion.