Lecture 18 ECEN5341/4341 March 2, 2015

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

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 1. Nerves and Action Potentials 2. Activate Mussels 3. Effect Growth Processes. 4. Involved in Memory

Standard Nerve Cell Model 1

Cell Membrane Cartoon

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 2. For J=0

Active Pumps to Maintain Concentration Differences 1. Na +, K + pumps 2. Many other pumps for 80 substances? – Ca 2+, 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 1. Triggered by influx of Na + as summed by the inputs from the dendrites at the cell body 2. Terminated by 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 On the Web Human Physiology - Cell structure and function for some good pictures and standard model with channels for Na, KHuman Physiology - Cell structure and function

Outline of Material 1. Problems with the current model for cells 2. Some properties water, H 2 O, 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 2. the concentration ratios and voltages are still there when the membrane is removed. 3. You can still get an action potential to propagate along a nerve cell with no Na or K if you have enough Ca. 4 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 0 o C water ρ=1 8. Water near proteins is structured. Hydrogen bonds in water ΔE=0.13eV/molecule to 0.21eV/molecule. Thermal Energy kT≈ eV 1Kcalorie/mol=0.043eV/molecule

Proteins 1. Have hydrophobic surface areas that induce bonding of neighboring H 2 O 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 H 2 O for charged sites. – Ions in about 1 in 500 charged sites. H 2 O 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 - >NO 3 - 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 H 2 O 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 H 2 O to force surfaces farther apart.

Phase Change And Action Potentials 1. Can be triggered by Na + displacing Ca ++ or other larger ions and also H 2 O 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 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 H 2 O

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 H 2 O can flow in. The cytoskeleton can store some energy elastically. 4. To terminate the pulse the H 2 O must exit and the Ca ++ return. 5. This is thought to occur destabilizing the structure of the water by the charges on the Na +