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The Sodium-Potassium Pump

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Presentation on theme: "The Sodium-Potassium Pump"— Presentation transcript:

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

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