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Lecture 5 B60 FA24

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Lecture Outline
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Setting the Stage: The cast of chemicals
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Fluid Composition
Phospholipid Membrane
Proteins
Movement of Ions
 At rest, the cytosol (intracellular) along the
inside surface of the membrane has a
negative electrical charge compared to the
outside
◦ Referred to as the Resting Membrane Potential
 Understand the Three Main Players
◦ Salty Fluids on either side of the membrane
◦ The Membrane itself
◦ The Proteins that span the membrane
δ
 Water
◦ Polar Covalently bonds
◦ Effective solvent for other charged or
polar molecules
◦ Key ingredient in intracellular and
extracellular fluid
◦ Key feature = uneven charge
δ
δ

Ions
◦ Net electrical charge
◦ Dissolve in water because
the charged portions of the
water molecule have a
stronger attraction for the
ions than they have for each
other
◦ A sphere of water molecules
surrounds each ion (spheres
of hydration)
◦ Insulate the ions from each
other
◦ Monovalent vs divalent
◦ Cations (net +’ve charge)
◦ Anions (net -’ve charge)
 Ions are the major charge carriers involved
in the conduction of electricity in biological
systems (including neurons)
 Ions of particular importance for cellular
neurophysiology:
◦ The monovalent cation Na+ (sodium)
◦ The monovalent cation K+ (potassium)
◦ The divalent cation Ca2+ (calcium)
◦ The monovalent anion Cl- (chloride)
 First a review of terms
◦ Hydrophilic
 Dissolve in water due to uneven electrical charge
(e.g., salt)
 Water loving
◦ Hydrophobic
 Does not dissolve in water due to even electrical
charge (e.g., oil)
 Water fearing
◦ Lipids are hydrophobic
 Are a class of water-insoluble biolgoical molecules
important to the structure of cell membranes
 Contribute to resting and action potentials
Phospholipid bilayer is not
permeable to ions
 Each ion has a different
chemical concentration inside
and outside of the cell
 Each ion has an electrical
charge

BARRIER
A Few Quick Questions
QUESTION: How are electrical signals generated?
A Few Quick Questions
QUESTION: How can a change in ion permeability occur?
A Few Quick Questions
QUESTION: What are the Four major types of selective
ion channels in the neuron?
A Few Quick Questions
QUESTION: What are the 3 activation stimuli to open or close a
channel?
 Type and Distribution of Protein Molecules
distinguish neurons from other types of
cells
◦ Enzymes
◦ Cytoskeleton
◦ Receptors
◦ Special transmembrane proteins
 Control resting and action potentials

HYDROPHOBIC
HYDROPHILIC
Every amino acid
has in common:
◦ a central alpha
carbon
◦ An amino group
◦ A carboxyl
group
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Variability for
amino acids
comes from the
R group
20 different
amino acids to
make proteins
Assemble into
chains
connected by
peptide bonds
Form
polypeptides
Primary structure is the sequence of amino acids in the
polypeptide
 Secondary structure is the coiling of a polypeptide into a
conformation such as an alpha helix
 Tertiary structure is the three-dimensional folding of a
polypeptide
 Quaternary structure is when different polypeptides bond
together to form a larger protein
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
ION CHANNELS
◦ Typically requires 4-6 similar
protein molecules assembled
to form a pore between them
◦ Composition varies and
determines their properties
 Diameter of pore and nature of
R groups determines ION
SELECTIVITY
 Also determines GATING
properties
 Changes in the local
microenvironment of the
membrane can cause these
channels to be opened or
closed
ION PUMPS
 Formed by membrane spanning
proteins that use ATP to transport
certain ions across the membrane
 Critical role in neuronal signaling
by transporting Na and Ca from
inside to outside neuron
 1.
Diffusion
◦ Dissolved ions distribute
evenly
◦ Ions flow down
concentration gradient
◦ Channels permeable to
specific ions
◦ Concentration gradient
across the membrane
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2. Electricity
For electrically charged particles (such as
IONS), an electrical field can also be used to
induce the ions to move
◦ Opposite charges attract
◦ Like charges repel
Net movement of sodium toward the
negative terminal (cathode)
Net movement of chloride toward the
positive terminal (anode)
The movement of electrical charge is the
ELECTRICAL CURRENT
Positive current
2 Important Factors Affect Current Flow

ELECTRICAL POTENTIAL (voltage, V)
o The force exerted on a charged particle
◦ Reflects the difference in charge between the anode and
the cathode
◦ As the difference increases, more current will flow
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ELECTRICAL CONDUCTANCE (g)
o The relative ability of an electrical charge to migrate
from one point to another
◦ Depends on:
 the number of particles available to carry electrical charge
 the ease with which these particles can travel through space
o Electrical Resistance (R) is the same property
expressed in a different way
◦ The relative inability of an electrical charge to migrate
OHM’S LAW: I = gV
the amount of current equals the product of electrical conductance and
electrical potential. Note I = amount of current that will flow
 What will happen if the conductance is zero?
Remember Ohm’s Law
V= IR
then
Iion = gion (Vm-Eion) where
Iion = ionic current
Vm = membrane potential
Eion = equilibrium potential for the ion
gion = conductance
Difference Vm-Eion is the electrochemical
driving force acting on the ion
 We have electrically charged ions in solution
on either side of the neuronal membrane
 Movement of any ion through its channel
depends on the concentration gradient and
the difference in electrical potential across
the membrane
 Let’s explore further
 Membrane potential: Voltage across the
neuronal membrane
Bear video link
 Let’s review K+ equilibrium
 Equilibrium Potentials
◦ No net movement of ions
when separated by a
phospholipid membrane
◦ Equilibrium reached when K+
channels inserted into the
phospholipid bilayer
 Equilibrium Potentials (Cont’d)
◦ The Nernst Equation Box 3.2
 Calculates the value of an equilibrium potential in
mV
 Takes into consideration:
 Charge of the ion
 Temperature
 Ratio of the external and internal ion concentrations
 NOTE: you will not be asked to use the Nernst
equation in this course
 E ion = 2.3 RT/zF log[ion]outside/[ion]inside
 E ion
ionic equilibrium potential
 R
gas constant
 T
absolute temperature
 Z
charge of the ion
 F
faraday’s constant
 Log base 10 logarithm
 [ion] inside or outside of the cell
 K channels
◦ K+ channels: 4 subunits
◦ Channel selectively
permeable to K+ ions
◦ MacKinnon—2003 Nobel
Prize
 Mutations of specific K+
channels; Inherited
neurological disorders eg:
weaver mouse
• a strain of mice that has difficulty maintaining posture
and moving normally.
• defect has been traced to the mutation of a single AA in
the pore loop of a potassium channel found in specific
neurons of the cerebellum.
• mutation allows Na as well as K can pass through the
channel
Examples of K channels
Structure of a simple bacterial K+ channel determined by crystallography

The Distribution of Ions
Across The Membrane
Note: E ion is the membrane potential that would be
achieved at body temperature if the membrane were
selectively permeable to that ion

The sodium-potassium pump
◦ Enzyme - breaks down ATP when Na present
◦ Calcium pump: Actively transports Ca2+ out of
cytosol
Characteristics of Resting Potential
 large proteins contribute to the negative
electrical potential
 Na+ 10Xs more concentrated outside than
inside
 K+ 20Xs more concentrated inside
 K+ and Cl- remain open allowing both ions
to flow through; Na+ gates remain closed
 Na+-K+ pump transports Na+ outside of the
cell while drawing K+ into the cell
 RP of a neuron provides a baseline level of
polarization
 Relative Ion
Permeabilities of the
Membrane at Rest
◦ The importance of
Regulating the External
Potassium
Concentration
 Depolarization
 What happens if cell
depolarizes?
Increasing extracellular potassium depolarizes neurons
 Relative Ion Permeabilities of the Membrane
at Rest
◦ Neurons permeable to more than one type of ion
◦ Membrane permeability determines membrane
potential (changes)
◦ Goldman equation
 Takes into account permeability of membrane to
different ions
WHY is the average resting membrane potential for NEURONS -65 mV?
To answer this question, we need to combine all the equilibrium potentials of all
the ions and take into account their permeability (their ability to move across the
cell membrane)
The GHK Equation (box 3.3)
Vm = 61 log Pk[K+]out + PNa[Na+]out + PCl[Cl-]out
z
Pk[K+]in PNa[Na+]in
PCl[Cl-]in
The GHK equation predicts membrane potential using multiple ions
 Relative Ion
Permeabilities of the
Membrane at Rest
◦ The importance of
Regulating the External
Potassium
Concentration
 Blood-Brain barrier
 Potassium spatial
buffering
1. RP is the consequence of the differential
concentrations of ions inside and outside the
neuron, AND the semipermeable nature of the
membrane
2. Membrane is primarily permeable to K ions.
When equilibrium is reached between the
diffusion pressure forcing K out of the cells, and
the electrostatic pressure forcing K into the cell,
RP is -60 to -70
3. Neurons must actively maintain this ion
balance via the Na/K pump due to the gradual
leakage of ions across the membrane
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