1. The Sodium-Potassium Pump
Consists of molecules in the neuronal membrane
Exchanges NA+ ions for K+ ions across the membrane
Requires energy for active transport of ions across the membrane

2. Membrane Permeability Determines Membrane Voltage

3. Membrane Voltage Determines Membrane Permeability

4. Stimulator
+++
Depolarize the Neuron

5. Question:
Why does a voltage change across the
membrane change membrane permeability?
Answer:
There are voltage-gated ion channels
embedded in the membrane.
a. Proteins in the membrane
b. 100,000 ions/sec can pass through
c. Squid axon: NA+ channels in
1.0 square micron of membrane
d. Selectivity filter and gate

6. Sodium Channel Blockers
Tetrodotoxin - Pufferfish ovaries
Scorpion Toxin
Batrachotoxin - South African frog

7. Potassium Channel Blocker
Tetraethyl Ammonium (TEA)
Calcium Channel Blocker
Cobalt

8. Question: How do we know that a voltage
change across the membrane opens
ion channels?
Answer: The Patch-Clamp Technique

9. Llinas, 1992
Visualized calcium entry into terminal bouton
Giant Squid axon
Inject bouton of axon with jelly fish protein
protein emits light when it binds with Ca++
Experiment
a. Stimulate the axon to cause action potential
b. Detected rapidly flicking spots of light in
bouton at transmitter release sites

10. Transmitter-gated Voltage-gated
Channels Channels
Transmitter binding to Na+ Channel opens
receptor
Opens NA+ channel Additional Na+ inflow
Na+ inflow Depolarization reaches
Threshold
Depolarization
Action Potential

11. Two Different Systems of Neurochemical Transmission
Small molecule neurotransmitters
Synthesized in terminal bouton
Short-lived effect on receptor
Large molecule neurotransmitters
Peptides (chains of amino acids)
Synthesized in cell body
Transported in vesicles to bouton

12. G-protein linked receptor
G- protein has a subunit (alpha subunit)
induces
second messenger synthesis
Bind to ion
channel influence enter nucleus
neuron metabolic
activity gene expression
Open or close
channel
Protein synthesis

13. Transmitter - receptor Binding
Two General Receptor Types
1. Ion-channel linked receptor
- Ionotropic
2. G-protein linked receptor
- Metabotropic

14. Neurotransmitters
Acetylcholine (ACh)
Monoamines
Epinephrine - adrenaline
Norepinephrine - noradrenaline
Dopamine
Serotonin
Amino acids
Peptides
Gases

15. Acetylcholine(ACh) - Soma locations
1. Spinal motor neurons Skeletal muscles
2. Septum Hippocampus
3. Nucleus Basalis Cortex
4. Vagus nerve Smooth muscles (internal
motor neurons organs-e.g., heart)
5. Interneurons

16. Biosynthesis of Acetylcholine
Acetyl coenzyme A
(acetyl CoA)
Coenzyme A
(CoA)
Acetate ion
Acetylcholine
Choline
Choline
Acetyltransferase
(CAT)
enzyme

17. Two Types of ACh Receptors
1. Muscarinic Receptor
smooth muscles (e.g., heart)
brain neurons
G protein-linked or metabotropic receptor
muscarine = agonist
atropine = antagonist

18. 2. Nicotinic receptor skeletal muscles brain neurons
ionotropic receptor
nicotine = agonist
curare = antagonist

19. Antagonists of ACh Transmission
1.Clostridium Botulinum
- bacteria in poorly canned food
- produces botulin neurotoxin
- inhibits ACh release
2. Black Widow Spider Venom
- venom = protein
- binds with bouton membrane
- forms a pore
- CA++ enters the pore
- depletes neurotransmitter

20. 3. Cobra Venom
- venom = protein
- binds to nicotinic receptor
- prevents ACh binding to receptor
4. Organophosphates
- irreversible acetylcholinesterase (AChE)
inhibitors
- nerve gas
- prevent breakdown of ACh
- promotes receptor desensitization
ion channels close despite high ACh levels

21. Myasthenia Gravis Autoimmune disease
antibodies against nicotinic ACh receptor
receptor number reduced
clinical symptoms
- muscle weakness (eyelids, limbs, respiration)
treatment
- physostigmine = AChE inhibitor

22. Monoamines Dopamine Norepinephrine Epinephrine Tyrosine L-Dopa
Released from varicosities

23. Dopamine Substantia Nigra Receptors Soma locations
Ventral Tegmental Area (VTA)
Receptors
5 subtypes (D1 - D5)

24. Norepinephrine Soma locations Locus coeruleus Receptors
Beta (B1. B2, B3)
Alpha (A1, A2)
Epinephrine
Medulla

25. Serotonin (5-HT) Tryptophan 5-hydroxytrytophan (5- HTP)
5-hydroxytryptamine (5- HT)
(Serotonin)

26. Serotonin
Soma locations
Raphe nuclei
Receptors
15 subtypes

27. Amino Acids
1. Glutamic acid (glutamate)
- main excitatory neurotransmitter
Soma locations - Everywhere
Receptors
10 subtypes

28. Amino Acids - continued 2.Gamma-aminobutyric acid(GABA)
- main inhibitory neurotransmitter
Soma locations - everywhere
Receptors
two types
GABA A - Chloride channel
Benzodiazepines -Valium
Librium
GABA B

29. Neuropeptides Enkephalins Vasopressin Oxytocin Substance P
Cholecystokinen
Neurotensin
Somatostatin
Neuropeptide Y
Vasoactive intestinal peptide
Angiotensin
Corticotropin-releasing factor
Beta-endorphin

30. Soluble Gases Nitric oxide Carbon monoxide - Do not bind to receptors
- diffuse into neurons
- activate second messengers