Download General questions about ion channels

Key Review Points:
1. Electrical signaling depends on the motion of
ions across neuronal membranes
2. Na+, K+, Cl- and Ca++ ions are distributed
unequally across neuronal membranes
3. At rest, diffusion of these ions creates the
membrane potential
4. Rapid changes in ionic permeability cause
transient, self-regenerating changes in the
membrane potential known as action
potentials, which carry information
Today’s Lecture:
Ion channels: proteins that form pores in the membrane
to permit ions to cross
Ion transporters: proteins that actively transport ions
across membranes to establish concentration
gradients
New technology: The patch clamp technique
The voltage clamp
technique shown before
was adequate for large
currents, but produced
large ‘background
noise’
‘Patch clamp’ technique
has superior signal-tonoise ratio, so very small
currents can be measured,
even down to the current
passed through a single
ion channel!
Early sodium current
during the action
potential is due to the
aggregate action of
many individual
sodium channels
Later potassium current during
the action potential is due to
the aggregate action of many
individual potassium channels
Voltage dependence of open Na+ and K+ channel open
probabilities mirrors the voltage dependence of Na+ and K+
conductances
Voltage-dependent Na+ and K+ channels
General concept
General questions about ion channels
How can a protein sense voltage?
How does it respond respond with the appropriate timing?
How does it permit some ions to cross the membrane
while excluding others?
How does it inactivate?
--> Functional studies of ion channel proteins
Need to express ion channels in cells, in isolation from other channels:
The Xenopus oocyte electrophysiology technique
Types of ion channels
Further diversity gained through alternative splicing, editing,
phosphorylation, mixing and matching of different subunit
types
Functional diversity
Example: K+ channels
Nearly 100 known
Examples of functional
variations:
Molecular architecture of ion channels
X-ray crystallography reveals mechanisms of ion permeation,
selectivity
KCsA bacterial ion channel
Geometry of negative charges, pore size, and ion hydration work
together to provide K+ selectivity, excluding Na+
Mechanism of voltage sensitivity
TM4 contains charged residues; these move in the
membrane when membrane potential changes
Human neurological diseases are caused by ion channel mutations
Kinetic properties of ion channels are finely-tuned, alteration of
them causes disease
Ion transporters:
Proteins that actively transport ions across membranes to
establish concentration gradients
Na+ efflux from the squid giant axon:
Sensitive to removal
of extracellular K+
Sensitive to block of
intracellular ATP
generation
Usually, the Na+/K+
ATPase has only a small
direct effect on
membrane potential, (<1
mV) because it is very
slow compared to ion
flux through ion
channels
However, it can have a
larger effect if in smalldiameter axons, where
the ratio of surface-area
to cytoplasm volume is
small and ion
concentrations change
appreciably
Transporter structures
Na+/K+ ATPase, deduced by mutagenesis
The Ca++ pump: a more structure-based view