- Selective breeding of plants and animals 

- The diversity of living organisms is understandable in terms of evolution and natural selection

- The origin of species 

- Cricks grandfather sent him the material for his study on freshwater bivalves 

- Traits segregate and sort in an orderly fashion during reproduction 

- Most famous experiment = peas 

- showed that characteristics of peas could be selectively bread and would inherit in a very quantitatively organized way 

- Genes underlie traits 

- Genes are Molecules

- Gene Mutation 

- "On the nature of Gene Mutations and Genes"

- "Part Three : Atomic PHysics Model of Gene Mutation"  

- Crystallization of tobacco mosaic virus

- UCB  

- Virus is a simple structure made of just protein and nucleic acid that has genes in it 

- The crystalization showed that it is mostly genes and therefore the genes have some kind of molecular regularity 

- suggestive that genes are molecules 

-Wrote a book "What is life"

- one of the main formulators of mathematical structure of quantum mechanics 

- Inspired Francis Crick and James Watson 

-  "What is life"

- Thought that molecular probing of life might lead to new knowledge of nature and laws of physics 

- Implicitly demonstrated in the Journal of Experimental    Medicine that DNA carries genetic information 

- Did not fit with people's conception at the time that genetic code involved proteins/ amino acids 

- Noble prize in chemistry 

- Concerned with spread of radioactive materal in nuclear testing

- tried to limit atomic weapons development 

- Wrote about Vitamin C as a treatment for common cold 

- Labeled Communist

- Unworkable structural model of DNA

- Thought DNA was a triple Helix

- Worked in uranium isotope separation for the Manhattan project

- something about atomic bombs 

- the fundamental unit of heredity 

- sequence of nucleotides (A, G, C, T) in DNA 

Adenine

Guanine

Cytosine 

Theymine (becomes uricil in mRNA)

- The relationship between DNA nucleotides and the amino  acids in proteins 

- (3 nucleotides (codon) = 1 amino acid)

- 

Mostly water

- within water is mostly ions

- Various membrane proteins permit and regulate ion movement across biological membranes 

- Channels 

- ATP- dependent pumps 

- other transport proteins 

** Difference ( if a channel is open then ions will flow through from a place with more concentration to a place with less concentration. ATP pumps move things from a place with less concentration to a place with more concentration. The energy itself is called ATP)

- Adenosine Tri-phosphate 

- intercellular energy currency 

- energy storage in phosphate bonds 

- called so because of molecular components :

1. Adine (central piece)

2. Ribose Sugar

3. Phosphate groups

- Cells spend energy to make ATP and then this ATP folats around and does various things inside the cell 

- Used to move ions from one side to the other against their concentration gradient 

Sodium/ Potassium Pumps 

(Na+/ K+)

- Pumps Na+ out of neuron 

- Pumps K+ into the neuorn 

- uses ATP as an energy source because it is doing   this constantly

- 1 ATP used =

- 3 Na+ out 

- 2 K+ in 

Na+ outside > inside

K+ outside < Inside 

Cl- outside > inside 

Ca ++ outside > inside 

** Everything is more concentra

 intracellular and extracellular ion concentration differences 

- inside of the cell is more negative and the outside of the cell is more positive 

Hyperpolarization 

Cell becomes more negative (more polarized relative to the resting potential) 

This can happen when a K+ opens because the potassium flows out

OR a chloride channel can open and chloride will flow IN and this will cause a more negative charge inside 

Opposite case of hyper polarization (more to a more positive level) 

A channel can open that allows sodium to flow through

carries positive charge inside making the inside less negative

This would also happen if a calcium ion opened for the same reasons 

- Changed the thinking of electricity and the body 

- "Animal Electricity" - muscles move as a result of internal electrical forces that can be triggered by external electrical stiumlation 

- frog legs

- because of his work the whole idea of electricity and life and nervous system kinda took off 

Appreciated the large size of squid axons

- Recorded an action potential from inside the axon

- Happened at the same time as WWII,

called to help and had to drop everything for about 6 years

- Predicted existence of channels  

- Ion channels are closed at resting potential 

- when voltage changes they will either open or close 

- when membrane voltage changes then the force of the tug changes, it can pop open ions 

- Resting potential = -70mV

- Both Na+ and K+ closed 

- Na + open and there is a depolarization at the top of the peak at +40 mV

- Re-polarization occurs ( K+ open  (around 30 mV) and Na+ close)

- Hyperpolarization (-80 mV) (k+ open)

- Layers of lipid-bilayer membrane cross-linked by proteins 

- Very thick boundary layer 

CNS:

Ependymal cell

Astrocyte cell 

Microglial cell 

Oligodendrocyte cell 

PNS:

Schwann cell 

Discovered myelin and the nodes of Ranvier 

French physician and anatomist 

- The gaps between myelin = the nodes of Ranvier

- Saltar = to dance 

- action potential in mylenated axon

- action potential jumps from one something to another  

Demyelinating Disease 

- Multiple Sclerosis 

- Auto-immune damage to myelin 

- unknown cause 

theory "body's own immune system starts attacking myelin

- Nerve conduction impaired 

Too much water

low sodium 

Dilution of ions essential for function of nervous system 

Paracelsus 

** KNOW HOW TO SPELL**

- Protective barrier around the CNS

- tight junctions between cells forming the blood vessal walls 

 **formation of tight junctions facilitated by astrocytes 

- blocks voltage gated sodium channels 

- no nerve signals can be sent 

- a chemical produced by bacterial living symbiotically with these animals 

* puffer fish * octopus (blue ringed)

* some starfish and Crabs

* blow fish 

* fungi 

* newt/ salamander 

- peripheral nerves unable to generate normal action potential 

Symptoms: numbness, muscle weakness, paralysis 

Death = respiratory paralysis 

* DOES NOT CROSS BLOOD BRAIN BARRIER 

-- does not get into the brain 

Lipophilic/hydrophobic molecules 

a few molecules that are transported (Glucose sugar and some amino acids) 

- May result from changes in only a single amino acid in the voltage gates Na+ ions 

- ( one out of ~ 1800 amino acids)

- produces a large decrease in binding affinity (stickiness) of TTX for the Na+ channel proteins 

- When dinoflagellates bloom during the red-tide shell fish fed on them. 

- shellfish eat them and can accumulate their saxitoxin without dying 

- Now the shell fish have the poison and we eat it and can get sick

Condition that saxitoxin produces

- People eat shell fish and can get sick 

- SAME SYMPTOMS AS TTX:

numbness, muscular weakness, paralysis 

DEATH: respiratory paralysis 

attaches to voltage gated sodium channels and blocks it

** DOES NOT STOP HEART

** DOES NOT CROSS THE BLOOD BRAIN BARRIER 

therefore doesn't enter the CNS 

Results from mutations that change amino acids in the voltage gated sodium channel 

- SAME AS TTX

- subtle changes in protein structure

Toothache Drops 

- first thing to be identified as a local anesthetic 

- comes from coca plant in South America 

- grown originally for its leaves to make tea and to be chewed making it a mild stimulant 

- first discovered in the 1800s 

- local anesthetic 

Numbs sensation locally 

COCAINE

doesnt work on the brain, only works on the specific area 

- Interferes with normal opening/closing action of voltage-gated Na+ channels so when the voltage changes to pop-open there is a change so that it wont 

(Phyllobates Terribilis) Tree Frogs 

- in the amazon jungles of south america darts are dripped in their poisonous secretion

- used to shoot and capture animals by hunters  

- BTX prevents CLOSURE of voltage gated na+ channels 

- not really sure where it is from but maybe beetles ? 

- associated with consumption of a variety of fish 

- probably produced by dinoflagellates 

- produces a lowering of the threshold voltage for the opening of the channel 

-**TAKES LESS exictation for the voltage gated na+ channel to open 

( aka easier to open)

Symptoms:  Nausea, vomiting, diarrhea, abdominal pain, muscluar pain 

Over view of TOXINS

(Various ways of interfering with the voltage-gated sodium-channel function)

- Tetrodotoxin 

- Saxitoxin 

- Local Anesthetics

- Batrachotoxins - channels stuck open

 - Ciguatoxins- threshold for opening is lowered 

Ramon y Cajal 

(The neuron Theory)

- Had a discrete concept of neurons 

- thought that there was a dircetino that signaling wen                    

receiving into dendrite and sending them out the axon 

- also used Golgi's stain to look at things 

- much more accurate 

Camillo Golgi 

(The Reticular Theory)

- used a stain to look at neurons in the brain 

- came up with this staining process himself 

- based on his drawings he thought that here was a big web in the brain and everything was all interconnected and signals could be sent any which way

- Synapse = means to clasp together 

- involves the release of neural transmitters from the end of the axon 

Electrical Synapse 

( Gap Junction )

- what we need to know about 

- direct connection between the two neurons (VERY SMALL GAP)

- CONNECTION VIA CHANNEL PROTEINS (connexons)

which allow ions to flow through 

- a lot of neurons in the brain are connected this way 

- Frog Hearts 

- woke up in the middle of the night and wrote down his dream which was the idea for his famous experiment 

- Put frog hearts in jars of salt water

- electrically stimulated the hearts 

- discovered the first neurotransmitter mocule **(acetylcholine ACh)

- demonstrated chemical signaling

 - if you can generate some action potential in the vagus nerve then the heart slows down 

- he collected fluid from the stimulated hearts and transferred it to another heart that was already beating 

- when he did this THAT heart slowed down 

- this showed that there was a chemical reaction through the SOLUTION

Vagus Nerve

Comes out of the brain stem 

- Parasympathetic connection to the hear 

- one of the cranial nerves 

• Action Potential
• Voltage-aged Ca++ channels open 
• Vesicle Fusion 
• Neurotransmitter release 
• binding to receptors 
• this carries signal into the next cell 

Either by being taken back up into the axon terminal

or chemically inactivated

- Reuptake transporter proteins 

- Enzymatic degradation 

Proteins in the axon terminal that recycle the neurotransmitters and put them back into the cell 

- returns to where it came from so it can be resued 

Lipid bilayer spheres 

- bind onto the end of the axon terminal and release neurotransmitters 

Neurotransmitters 

(General)

- Have reuptake trasnporters 

- have synaptic storage vesicles

- and can possibly release neurotransmitters 

- has a permanent positive charge 

- Does not cross the blood brain barrier 

- because VERY polar 

- it is used in the brain but is not capable of getting into it

* Neurotransmitter in :

1.Parasympathetic nervous system 

2. Neuromuscular Junction (connection between nerves and muscles)

3. Brain 

Ionotrophic and metabatrophic 

* Nicotinic AChR = inotrophic (na+channel)

tobacco plant

* Muscarainic AChR = metabotropic / GPCR

Mushroom 

Doesnt cross blood brain barrier 

There are a relatively small number of clusters (speaking relatively)  located in the brain stem that are the source of ACh

Acetylcholine Esterase (AChE)

Breaks down Acetylcholine 

- an AchE inhibiter results in an over activity of acetylcholine 

**used as a drug for dementia 

- broken down into 

 1. Acetate 

 2. Choline 

Pieces take back up separately by reuptake transmitters and then put back together in the cell 

**If you inhibit acetylcholine esterase then there is TOO MUCH STIMULATION which is very poisonous 

 --> Pesticides 

EPSPs

(Excitatory Post-synaptic potential)

- depolarization 

- when the channel opens, sodium or calcium flows through making the inside of the post synaptic cell more positive 

- if you have multiple channels opening then their effects add together add together and push the membrane close to the threshold for firing an action-potential

how action potentials get started  

IPSP

(Inhibitory Post-Synaptic Potential)

-hyperpolarization 

- Does the same as the EPSP but the opposite 

- makes the inside more NEGATIVE

- uses potassium or chloride 

- moving AWAY from the threshold 

** anything that is hyperpolar is inhibitory 

Glutamate 

(Glutamic Acid)

PRIMARY EXCITATORY neurotransmitter in the human brain 

- amino acid (Nh2)

- one of the building block amino acids for proteins 

- bonds to ca+ and na+ 

- makes inside of cell more positive and more excitatory 

**ionotropic glutamate receptors are CA++ and Na+ channels 

**makes GABA

--> all cells have glutamate 

GABA

- Gamma-Amino-Butyric Acid 

- primary INHIBITORY nt in the human body 

- ionotropic GABA receptors are Cl- channels 

-pulls away from threshold of action potential and binds to Cl- 

**GABA is made from glutamate 

Metabotropic Receptors 

(GPCRs)

Raphé means seam 

- relatively small number of serotonin making molecules in the brain 

- ANOTHER NAME for serotonin is 

5- hydroxytryptamine 

- chains of amino acids 

(endorphins = opioid peptides)

- First discovered in a powered perpetration of a cows stomach 

- 11 amino acids long 

- found all over the brain 

- in spinal cord and digestive system 

- Amino acids : glutamate , GABA, gylcine 

- Made from Amino Acids : seretonin, dopamine, norepinepherine , epinepherine, histamine

- Small Molecules : acetylchole, adenosine, ATP

- Peptides : endorphones , substance P

- Others

- Glutamate  : inototropic & GPCR

- GABA : inotorpic & GPCR

-Acetylcholine : Inotropic & GPCR

- Serotonin : Ionotropic &GPCR  (**all but one are GPCR)

dopamine 

epinepherine 

histamine

adenosine

ATP

endorphins 

substance P

** LARGEST DIVERSITY OF RECEPTORS IN THE BRAIN