Lecture 18 ECEN5341/4341 February 25, 2016

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Lecture 18 ECEN5341/4341
February 25, 2016
Nerve Cells
• 1. Neurons, generate voltage waves that carry
information from one place to another.
• 2. Glia Cells support functions of insolation
and clean up of unwanted materials
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A Neuron
Neuron
• 1. From a few to 200,000 Synapse as inputs.
• 2. Chemical flow may be unidirectional
• 3. Direct electrical connections with gap
junctions.
• 4. More than 40 neural transmitters that may
be both excititory and inhibitory
Electrical Signal In the Body
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1. Nerves and Action Potentials
2. Activate Mussels
3. Effect Growth Processes.
4. Involved in Memory
Standard Nerve Cell Model
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Cell Membrane Cartoon
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Cell Membranes
• 1 Classical nerve cell
– Na+outside =142mEq/L
1gr/dL=2.5mEq/L
– Na+inside = 14 mEq/L
– K+outside =4 mEq/L
– K+inside = 140 mEq/L
– Cl-outside = 103 mEq/L
– Cl-inside = 4mEq/L
– Enzymes also negative on the inside
2. Not included Ca++, H+, OH-,
Diffusion Potential
• 1. Basic equation
Ck
J  qCk E  qDk

x
2. For J=0
Ckout
Vm  VT ln
Ckin
kT
VT 
q
Vm  90mV
Active Pumps to Maintain
Concentration Differences
• 1. Na+ , K+ pumps
• 2. Many other pumps for 80 substances?
– Ca2+,Fe,I, Cl, Urea, sugars and amino acids
• 3. All require energy.
• 4. These all require protein channels.
• 5. Co-transport of molecules say Na +Glucose
into the cell.
Na+ , K+ Concentration Gradients
Relative Permeability of Membrane
Action Potential
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1. Triggered by
influx of Na+ as
summed by the
inputs from the
dendrites at
the cell body
• 2. Terminated by
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Outflow of K+
Na+ Gate
Channels
Current Pulses
Action Potential
• 1 Propagates at constant
– Amplitude for up to 3m
• at speeds up to 100m/s
• 2.Repeated and amplified
• at the nodes of Ranvier
Synaptic Junction Output
Neurotransmitters
Neural Transmitters
• 1. Neural transmitters move from presynaptic to
postsynaptic side of node on activation by an
action potential.
• 2. Receptor Proteins bind to neural transmitters.
• 3. Can open both ion and chemically activated
channels.
• 4. Voltage gate Ca++ released in postsynaptic
terminal by neural transmitters. 2,000 to 10,000
Ca++ ions.
Enzyme Receptors etc.
• 1. Much more going on.
• 2. Activation of metabolic machinery in cells
forming C-AMP which excites other processes.
• 3. Activate protein kinases which reduce
number of receptors.
• 4. Have both excitatory (Na+) and inhibitory
(K+, Cl-) processes.
A Different Approach to Cell Structure
and the Function of Membranes.
• 1. Reference
• Cells, Gels and the Engines of Life by Gerald H.
Pollack Published by Ebner and Sons Seattle
Washington. 2001
• 2 On the Web Human Physiology - Cell
structure and function for some good pictures
and standard model with channels for Na , K
Outline of Material
• 1. Problems with the current model for cells
• 2. Some properties water , H2O, Solutes , Ions
and cell potential
• 3. Properties of Gels and Cytoplasm ,
• 4. Phase Transitions a Mechanism for Action
• 5. Action potentials.
Some Problems.
• 1. Not enough energy for all the pumps.
• 2. Need 50 or more types of channels and pumps
• 3. The concentration ratios and voltages are still
there when the membrane is removed.
• 4. You can still get an action potential to
propagate along a nerve cell with no Na or K if
you have enough Ca.
• 5. You can get channel like pulses in inert
membranes.
Pulses Observed at a Membrane
Surface
Some Problems
4. Holes can stay open for 20 minutes to hours
and the cell does not die.
5. Proteins are about 50% of the membrane and
may be folded so that they contain
channels.
6. The Na+ concentration is higher near the
membrane than in the center.
More Problems
7. Cell can live at temperatures below that for
freezing water meaning that much of the water is
structured and bound to proteins and can exclude
Na+ . Pure water would expand enough to rupture
the cells. For ice ρ = 0.92 at 0oC water ρ=1
8. Water near proteins is structured. Hydrogen
bonds in water ΔE=0.13eV/molecule to
0.21eV/molecule . Thermal Energy kT≈ 0.026 eV
1Kcalorie/mol=0.043eV/molecule
Proteins
• 1. Have hydrophobic surface areas that induce
bonding of neighboring H2O molecules in
0.5nm pentagonal structures. These regions
are not soluble in water and are mostly in the
core.
• 2. Have Hydrophilic surfaces charged elements
that react strongly with water.
• 3. Protein surfaces are studded with charges
• Carbonyl (-),amino (+) side changes (+ or -)
Proteins
• 1. Ions compete with H2O for charged sites.
– Ions in about 1 in 500 charged sites. H2O dipoles
line up near charge sites
2. Charges alternate along the protein backbone
about every 70nm
3. This leads to a large fraction of the water in a cell
being structured by the proteins.
4. The distance between surfaces is about 5nm or
10 to 15 water molecules
Implications
• 1. Large molecules are less soluble than small
molecules in structured water except when
the structure fits.
• 2. This means the larger the size of the solute
the more it is excluded from the cell and the
larger the ratio of the concentration from the
outside to inside.
• 3. The interior of cell seems to be mostly a gel
with most of the water structured.
Implications
• 1. Ions are attracted to charges of opposite
sign but restricted by solubility or size.
• Bare Na+=9.5nm Bare K+=13.2nm
• Hydrated Na+=50nm Hydrated K+=36 to 40nm
• So the volume of Na+≈2x K+ so Na+ excluded to
the extent of 0.15 from the inside of a cut
nerve cell.
• Mg+>Ca++>Na+>K+>Cl->NO3- these are viscosity
measurements
Concentration as Function of Distance
from a Cut.
K+ Binding to Proteins
and Proteins Net Negative
• 1 Approximately 52% of K+ seems to be bound
to proteins
• 2. Give a K+/Na+≈20 in a cell cytoplasm
• 3. Protein charges 1.6mole/kg negative,
1.01mole/kg positive so net negative
0.6mole/kg
• 4. This means the interior of a cell is negative.
• 5. Some cells more negative some less. -70 to
-90mV Hemoglobin net negative – 10mV.
Phase Transitions in Gels
• 1. Small changes in the environment can lead to
phase changes in gels with big changes in volume.
Temperature, ph, electric fields, mechanical stress
– (Piezoelectric ?)
• 2. Uncharged surfaces 5:1 to 10:1 water layers
– Charged surfaces up to 3000:1 layers
3. Raising temperature can disrupt the structure, reduce
viscosity by opening spaces in the gel.
4. Phase changes cascade as two competing forces
become unbalanced.
Phase Transitions in Gels
• 1 Protein Protein attraction vs attraction for
H2O
• 2. Cooperative interactions lead to zipper like
changes.
• 3. E field contraction at one end and release
leads to a contraction wave that move
through the cell along the surface.
• 4. You can get self oscillations
Release of Molecules from Gels
• 1. Neural transmitters from Synapse can be
released with a phase transition.
– A. This can be explosive 2mm/sec and 600 fold volume
expansion
– B. This does not happen in water but can be triggered
by Na<10mM
– C. Can also be triggered by electric currents.
– D. Condensation by ordering of charged polynomials
– E. Expansion breaks down bridges and allows flow of
H2O to force surfaces farther apart.
Phase Change And Action Potentials
• 1. Can be triggered by Na+ displacing Ca++ or
other larger ions and also H2O
• 2. Problem with standard channel theory is that
you can still get an action potential with no
Na+ or K+ if you have enough Ca++
• 3. So these channels are not required for an
action potential to flow along the nerve cell.
• 4. The cytoskeleton is 100 time thicker than the
membrane and the current flows through both.
Action Potentials
• 1. The cytoskeleton is cross-linked actin
filaments and microtubules. They run axially
just below the membrane and have a large
negative charge.
• 2. Phase transitions in the cytoskeleton
– A. Release heat with raising voltage and absorb it
with falling voltages
– B. The action potential leads to cellular expansion
and the accumulation of H2O
Action Potential
• 3. Ca++is required for the cross linking of the
cytoskeleton. If the Ca++is replaced by a mono
charged ion (Na+ ,K+ etc.) then the lattice expands
and H2O can flow in. The cytoskeleton can store
some energy elastically.
• 4. To terminate the pulse the H2O must exit and
the Ca++ return.
• 5. This is thought to occur destabilizing the
structure of the water by the charges on the Na+
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