Psy 111 Basic concepts in Biopsychology

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Psy 111 Basic concepts in Biopsychology Lecture
3 The Membrane Potential
Website http//mentor.lscf.ucsb.edu/course/summer
/psyc111/
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Objectives

• Describe the electrical properties of (excitable)
  membranes.
• Describe the bases of charged molecules and their
  interactions with water and non-polar molecules.
• Identify the two forces which act on ions to
  control their movement diffusion and
  electricity.
• Discuss the principles of ion movement across a
  semi-permeable membrane and the electro-chemical
  equilibrium potential.
• Explain the Nernst equation and how alterations
  in ion concentration relate to equilibrium
  potential.
• Discuss the relation between equilibrium
  potential for an ion and the membrane potential.
• Discuss interactions between multiple ions within
  a cell/system, relative permeability and the
  Goldman equation.
• Discuss the proteins which control permeability
  channels and pumps.

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Objectives

• Describe the electrical properties of excitable
  membranes.
• Describe the properties and stages of the action
  potential.
• Define generator potential and threshold and the
  relation between the two including the relation
  between magnitude of generator potential and
  magnitude of neuronal response.
• Discuss relation of changes in membrane potential
  and relative permeability of KNa during the
  stages of the action potential.
• Identify the voltage-gated channels involved in
  the action potential and the properties of these
  channels.
• Describe relation between vg-Na channels and
  voltage sensitivity.
• Describe the positive feedback in generation of
  action potentials.
• Discuss role of vg-Na channel inactivation in
  conduction of action potentials.
• Explain the factors determining action potential
  conduction speed.

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Compartmentalization
Dendrites input Body protein
production Initial Segment integration Axon
conduction Terminal output
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Membrane potential
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Membrane Potentials in Excitable and
Non-excitable Cells.
Recordings from
Hepatocyte (non-excitable)
Neuron (excitable)
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Resting Potential Outline

• Ions, charges, water
• Forces acting on ions
• Principles of Movement of Ions Across a Selective
  Membrane
• Multiple Ions, Relative permeability, and the
  membrane potential.
• Control of Ion Movement

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The Basis of Biological Electricity Ions,
charges, water
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Ions, charges, water
Ions Valency net electrical properties Anions
net negative charge due to extra electron(s)
eg Cl- Cations net positive charge due to less
electron(s) eg Na Monovalent (e.g.
Na) Divalent (e.g. Ca) -gt Two parts valency
(more or less e-) magnitude (diff in e- verus
p)
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Ions, charges, Water
Water is a POLAR molecule with a separation of
charge such that oxygen is more negative and
hydrogens are more positive
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Ions, charges, water

• Many biological building blocks carry charge.
• This gives the macromolecule electrical
  properties.
• Charge is often distributed unevenly.

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Ions, charges, water
(containing components with distinctly different
properties)
e.g. phospholipid components of cell membrane
many proteins etc.
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Ions, charges, water
Phospholipids are amphipathic which is why they
form a bi-layer and why the bi-layer is a good
barrier.
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Outline

• Ions, charges, water
• Forces acting on ions
• Principles of Movement of Ions Across a Selective
  Membrane
• Multiple Ions, Relative permeability, and the
  membrane potential.
• Control of Ion Movement

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Forces acting on ions
1. Diffusion the movement of molecules down a
concentration gradient
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Forces acting on ions
Rate of Net Diffusion is proportional to
concentration difference
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Forces acting on ions
2. Electricity opposite charges attract and
like charges repel
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Ions across a membrane
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Electrochemical Equilibrium
At Electrochemical Equilibrium Electrical
force Rate of net diffusion

• Forces on a type of ion balance out
• Individual ions still move but there is no net
  movement.

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Ions across a membrane
K Permeable
Na Permeable

• Membrane potential is determined by selective
  permeability and the direction of the
  concentration gradient.
• the permeability and initial concentrations
  determine the direction of ion flow resulting in
  a relative charge distribution across the
  membrane.

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Outline

• Ions, charges, water
• Forces acting on ions
• Principles of Movement of Ions Across a Selective
  Membrane
• Multiple Ions, Relative permeability, and the
  membrane potential.
• Control of Ion Movement

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Principles of Movement of Ions Across a Selective
Membrane
1. Large changes in membrane potential are
caused by very small changes in ionic
concentration.   2. The net difference in
electrical charge occurs at the inside and
outside surfaces of the membrane.   3. Ions are
driven across the membrane at a rate proportional
to the difference between the membrane potential
and the equilibrium potential   4. If the
concentration difference across the membrane is
known an equilibrium potential can be calculated
for any ion.
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1. Large changes in membrane potential are caused
by very small changes in ionic concentration.
-per particle, the electrical force is much
greater than the diffusions factor. therefore,
changes in concentrations are negligible in
determining equilibrium.
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2. The net difference in electrical charge occurs
at the inside and outside surfaces of the
membrane.
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3. Ions are driven across the membrane at a rate
proportional to the difference between the
membrane potential and the equilibrium potential

• Vdiff I x g (Ohms Law)
• or
• I Vdiff / g
• Vdiff (voltage difference) is the driving force
  on a given ion and is determined by the
  difference in membrane potential (Vm) and its
  equilibrium potential (Eion).
• g (conductance) is determined by the net capacity
  of ions to move through a channel inverse of
  resistance (1/R).
• I (current) is the rate of flow of charge across
  the membrane.

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4. If the concentration difference across the
membrane is known an equilibrium potential can be
calculated for any ion.
Nernst Equation Eion 2.303 x RT x log
ionoutside zF
ion inside
R gas constant T temperature (consider always
37ºC) z valency of ion F Faradays constant
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If the concentration difference across the
membrane is known, an equilibrium potential can
be calculated for any ion.
Nernst Equation Add up constants R, T,
F Eion 61.54 x 1 x log ionoutside
z ion inside
Eion is the membrane potential at which the net
flow of the ion is 0.
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If the concentration difference across the
membrane is known an equilibrium potential can be
calculated for any ion.
Based on concentration of ions intracellulary and
extraceullary, which way does each ion tend to
move?
If the membrane is permeable to each ion then
what is effect on membrane potential (i.e. more
negative or positive)?
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If the concentration difference across the
membrane is known an equilibrium potential can be
calculated for any ion.
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5 mM 100 mM
-80 mV
150 mM 15 mM 101 62 mV
2 mM 0.2 µM 10,0001 123 mV
150 mM 13 mM 11.51 -65 mV
---- 108 mM ----- -----
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Practice questionsWhat happens with changes in
concentration?

• e.g. increase extracellular K
• increase extracellular Na
• increase extracellular Cl-
• Nerst equation only tells about equilibrium for 1
  ion
• Notice no ions will be at equilibrium at same
  time.
• But what determines the membrane potential (Vm)?

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Outline

• Ions, charges, water
• Forces acting on ions
• Principles of Movement of Ions Across a Selective
  Membrane
• Multiple Ions, Relative permeability, and the
  membrane potential.
• Control of Ion Movement

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Relative Permeability

• The ability of an ion to cross the membrane can
  be expressed relative to the ability of all other
  ions
• An ion that can cross more readily is said to
  have high relative permeability to an ion that
  passes less readily.
• Flow of ion(s) with high relative permeability
  contribute more to the membrane potential i.e.
  membrane potential will be close to the ions
  equilibrium potential.

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Relative Permeability

• Relative permeability serves to weight the
  contribution of an individual ion to the membrane
  potential which is mathematically incorporated
  into the Goldman equation as Pion
• The Goldman Equation
• Vm (61.54) log PK Kout PNa Naout PCl
  Cl-in
• PK Kin PNa Nain PCl Cl-out

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Relative Permeability
-Normally, K and Na are the main contributors
to Vm (can use a simplified Goldman equation) Vm
(61.54) log PK Kout PNa Naout
PK Kin PNa Nain -At rest membrane is
40 times more permeable to K than Na (i.e. PK
PNa x 40 so we can make PNa 1 and PK
40) Therefore, Vm (61.54) log 40(5)
1(150) -65mV 40(100) 1(15)
Now, what happens if relative permeability change?
How is this controlled?
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Outline

• Ions, charges, water
• Forces acting on ions
• Principles of Movement of Ions Across a Selective
  Membrane
• Multiple Ions, Relative permeability, and the
  membrane potential.
• Control of Ion Movement

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Control of Ion Movement
Channel passively allow ions to cross
membrane. Pump actively (requires energy) move
ions across membrane. Exchangers/transporters
use concentration gradient of one molecule to
move another molecule.
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Channels Structure

• Channels form a pore allowing ions to move across
  membrane
• Comprised of membrane-spanning domains (either
  one polypeptide or separate subunits).

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Ions, Channels, Microgradients
e.g. Na channels

• Channel Closed
• (at rest)

• Channel Opens
• (ions rush in)

3. Channel Closes (ions diffuses)
Botton (Inside) View
Side View
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Channels Permeability of Membrane

• Determination of total permeability
• Factors Influencing Movement of Ions through
  Channels
• 1. Number of channels
• -determined by gene expression
• 2. Single channel current I g V
• -intrinsic properties of channel
• 3. Probability of channel opening
• -intrinsic gating properties and modulated

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Pumps Primary Active Transporters
The major determinant in concentration
gradients are active transport systems (i.e.
pumps)
pump contributes to Vm 3 Na out for every 2 K
Note uses energy
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Transporters/Exchangers
In addition to carrying electrical charge, Ca
is an important signaling molecule within the
cell, thus, it is very tightly regulated.
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Glia Spatial Buffering
Astrocytes also contribute to ion concentrations
by regulating the extracellular levels of
Potassium Buffering.
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Resting Membrane PotentialSummary

• Membrane has a large relative permeability to K
  versus Na
• Membrane is impermeable to bulk of intracellular
  proteins (net anionic charge)
• Na/K Pump is electrogenic

Result is RMP - 65 mV
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Channel Gating Prelude to Action!

• Type of Gating
• Voltage
• Chemical
• Mechanical

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Electrochemical Equilibrium Membrane
Permeability for an Ion.
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Resting Membrane Potential Summary
Vm (61.54) log PK K0out PNa Naout PCl
Cl-out PK K0in PNa Nain PCl
Cl-in
At rest, membrane has a large relative
permeability to K versus Na
For our purposes there is a population of K
channels that are always open i.e. non-gated
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Membrane Potentials in Excitable Cells
Recordings from
Hepatocyte
Neuron
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The Action Potential

• Properties and description
• Relative permeablities
• Ion channels gating
• Conduction

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Description of AP stages
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Properties and description of the AP
AP Generation requires input Generator
Potential normally this is derived from
neurotransmission but can be experimentally
induced as depicted.
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Properties and description of the AP

• Generator potential must be of threshold value
  to generate AP
• Larger generator potentials increase frequency
  (not size) of APs

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Properties and description of the AP
Falling phase or repolarization corresponds to
absolute refractory period
Undershoot or hyperpolarization corresponds to
relative refractory period
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Properties and description of the AP
Increasing Generator potential increase AP
frequency Frequency can be increased only to
maximum 1000/Sec. -due to transient Absolute
refractory period
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The Action Potential

• Properties and description
• Relative permeablities
• Ion channels gating
• Conduction

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APs, Relative Permeabilites, Currents
Vm (61.54) log PK K0out PNa Naout
PK K0in PNa Nain
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• Rising Phase
• Inc. Na relative permeability
• Opening extra Na channels

Relative Permeability K Na Rest 40 1 Rise
40 400 Fall 100 1 Rest 40 1
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• Falling Phase
• Inc. rel perm of K
• Closing extra Na channels
• Opening more K channels

Relative Permeability K Na Rest 40 1 Rise
40 400 Fall 100 1 Rest 40 1
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Relative PermeabilityDynamics in an AP.
Relative Permeability K Na Rest 40 1 Rise
40 400 Fall 100 1 Rest 40 1
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The Action Potential

• Properties and description
• Relative permeablities
• Ion channels gating
• Conduction

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Ion Channels mediating APs
Two types of voltage-gated ion channels mediate
changes in membrane permeability during the
action potential Inactivating Voltage-gated Na
Channel Delayed (Rectifying) Voltage-gated K
Channel
Gated channels are those that undergo changes in
the probability of being open or closed resulting
in changes in relative permeablity of the
membrane to specific ions.
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Ion Channels

• Channels form a pore allowing ions to move across
  membrane
• Comprised of membrane-spanning domains (either
  one polypeptide or separate subunits).

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vg-Na Channels

• Inactivating
• Voltage-gated Na
• Channel
• single polypeptide
• four domains
• 6 transmembrane spans/domains
• voltage-sensitive
• selective pore
• inactivation gate

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vg-Na channels
Inactivating Voltage-gated Na Channel voltage-se
nsitive activation of selective pore is due to
modest depolarization
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Selective Pores
Only Na fits

• Na vs. K ions
• Equal charge
• Different hydrated sizes
• allows Na selective pore.

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vg-Na Channels
Inactivating Voltage-gated Na
Channel -voltage-sensitive activation
gate -inactivation gate
Removal of inactivation occurs only when membrane
repolarizes (ie at-65mV)
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vg-Na channels Blockade.

• Blockade of action potentials - no rising phase
  is possible.
• e.g. tetrodotoxin (TTX) from pufferfish

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vg-K channels

• Delayed (Rectifying) Voltage-gated K Channel
• four polypeptides
• four subunits
• 6 transmembrane spans/domains
• voltage-sensitive
• slow activation
• selective pore

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vg-K channels

• Selective pore as for non-gated K channel
• Similar vg mechanism as vg-Na channels

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Ion Channels during APs
Rest ng-K channels open vg-Na channels
closed vg-K channels -closed
Rise ng-K channels open vg-Na channels
open vg-K channels -closed
Fall ng-K channels open vg-Na channels
inactivate vg-K channels open
Rest ng-K channels open vg-Na channels
reset/closed vg-K channels close
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The Action Potential

• Properties and description
• Relative permeablities
• Ion channels gating
• Conduction

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Conduction of the Action Potential
-movement of AP from place to place along the
membrane.
What to do with a squid

• AP Generation in the axon hillock
• AP Conduction down the axon
• Conduction velocity and myelination

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Generation of AP in Axon Hillock
Axon Hillock (Initial Segment) -high in vg Na
Channels -high sensitivity (relative to dendrites
cell body) to generator potentials
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Generation of AP in Axon Hillock
Generator Potential reaches axon hillock
Act like a domino effect
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Generation and conduction of APs

• Density of voltage-gated Na channels determines
  sensitivity to depolarization
• Allows generation of AP (hillock)
• Conduction of AP (axon)

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Ions, Channels, Microgradients
e.g. Na channels

• Channel Closed
• (at rest)

• Channel Opens
• (ions rush in)

3. Channel Closes (ions diffuses)
Botton (Inside) View
Side View
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Conduction of AP down Axon
Goes in one direction due to inactivation gate on
proximal (toward soma) side of axon
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Conduction Speed
Speed is determined by conductance which is
proportional to volume, larger is faster and less
leakage (i.e. surface area versus volume).
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Myelination speeds up electrical
signal Saltatory conduction jumping of
electrical signal from node to node
Node of Ranvier
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Conduction Speed
Myelin serves to insulate axon reduces
leakage-gtstronger repulsion down axon-gtfaster
conduction