Psy 111211 Basic concepts in Biopsychology

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Psy 111/211 Basic concepts in Biopsychology Lectu
re 2 The Resting Membrane Potential
Website http//mentor.lscf.ucsb.edu/course/fall/p
syc111/
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Compartmentalization
Dendrites input Body protein
production Initial Segment integration Axon
conduction Terminal output
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Summary of Protein Synthesis
1. Transcription
2. Translation

• Post-translational processing

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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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Membrane potential
-relative net ionic differences between inside
and outside of cell with outside defined as 0.
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Membrane Potentials in Excitable and
Non-excitable Cells.
Recordings from
Hepatocyte (non-excitable)
Neuron (excitable)
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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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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 (this is why water
does not mix with oil which is non-polar).
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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
All molecules in solution are moving (i.e. have
kinetic energy) in a random fashion, thus, tend
to go from high concentration to low
concentration.
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Forces acting on ions
Rate of Net Diffusion is proportional to
concentration difference
Diffusion is very fast but is time dependent.
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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
Even in the presence of an electrical force, ions
can not pass through membrane unless passages
(e.g. protein channels) are present
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Electrochemical Equilibrium
At Electrochemical Equilibrium Electrical
force Rate of net diffusion

• Forces on a species (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.

Note A- presents net charge of proteins which
never cross 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, 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 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. -this is for a specific
type of ion. i.e. Na and K have different Eion
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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 in cytosol
(intracellular) and extraceullar fluid, 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.

Relative permeability serves to weight the
contribution of an individual ion to the membrane
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

Note in and out concentrations are reversed for
anions
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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
Neurons have three specialized types of membrane
proteins that control the movement of ions across
the membrane Channel passively allow ions to
cross membrane. Pump actively (requires
energy) move ions across membrane. Exchangers/tra
nsporters use concentration gradient of one
molecule to move another molecule.
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Control of Ion Movement Channels

• Channels are a family of structurally and
  functionally similar proteins.
• Form a pore allowing ions to move across membrane
• Comprised of membrane-spanning domains (either
  one polypeptide or separate subunits).

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Control of Ion Movement Channels
Protein channels provide for passive movement of
ions. -selective for specific ions. -open or
close.
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Control of Ion Movement Channels
Channel comprised of 4 subunits
K must loose spheres of hydration (surrounding
water molecules) to move through pore.
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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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Measuring ion movementPatch Clamping
In reality, channels open and close based on
probability the probability of some channels to
open or close can go up or down GATING.
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Control of Ion Movement

• 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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Control of Ion Movement Pumps
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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Control of Ion Movement Transporters
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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Control of Ion Movement Glia
Astrocytes also contribute to ion concentrations
by regulating the extracellular levels of
Potassium Buffering.
Start
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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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Prelude Channel Gating

• Type of Gating
• Voltage
• Chemical
• Mechanical