The Sodium-Potassium Pump Consists of molecules in the neuronal membrane Exchanges NA+ ions for K+...
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Transcript of The Sodium-Potassium Pump Consists of molecules in the neuronal membrane Exchanges NA+ ions for K+...
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
Question: Why does a voltage change across the membrane change membrane permeability?
Answer: There are voltage-gated ion channelsembedded in the membrane. a. Proteins in the membrane b. 100,000 ions/sec can pass through c. Squid axon: 100-600 NA+ channels in 1.0 square micron of membrane d. Selectivity filter and gate
Sodium Channel Blockers
• Tetrodotoxin - Pufferfish ovaries
• Scorpion Toxin
• Batrachotoxin - South African frog
Question: How do we know that a voltage change across the membrane opens ion channels?
Answer: The Patch-Clamp Technique
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
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
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
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 expressionOpen or close
channelProtein synthesis
Transmitter - receptor Binding
Two General Receptor Types 1. Ion-channel linked receptor
- Ionotropic
2. G-protein linked receptor
- Metabotropic
Neurotransmitters Acetylcholine (ACh) Monoamines Epinephrine - adrenaline Norepinephrine - noradrenaline Dopamine Serotonin Amino acids Peptides Gases
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
Biosynthesis of AcetylcholineAcetyl coenzyme A (acetyl CoA)
Coenzyme A (CoA)
Choline
Acetylcholine
Choline Acetyltransferase (CAT)
enzyme
Acetate ion
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
2. Nicotinic receptor skeletal muscles brain neurons ionotropic receptor nicotine = agonist curare = antagonist
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
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
Myasthenia Gravis
• Autoimmune disease• antibodies against nicotinic ACh receptor• receptor number reduced• clinical symptoms
- muscle weakness (eyelids, limbs, respiration)• treatment
- physostigmine = AChE inhibitor
MonoaminesDopamineNorepinephrine Epinephrine
Tyrosine
L-Dopa
Dopamine
Norepinephrine
Epinephrine
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Released from varicosities
Dopamine Soma locations Substantia Nigra
Ventral Tegmental Area (VTA) Receptors 5 subtypes (D1 - D5)
Norepinephrine Soma locations Locus coeruleus
Receptors Beta (B1. B2, B3) Alpha (A1, A2)
Epinephrine Soma locations Medulla
Amino Acids
1. Glutamic acid (glutamate) - main excitatory neurotransmitter
Soma locations - Everywhere Receptors 10 subtypes
Amino Acids - continued2.Gamma-aminobutyric acid(GABA) - main inhibitory neurotransmitter Soma locations - everywhere Receptors
two types
GABA A - Chloride channel Benzodiazepines -Valium
Librium GABA B
Neuropeptides Enkephalins Vasopressin Oxytocin Substance P Cholecystokinen Neurotensin Somatostatin Neuropeptide Y Vasoactive intestinal peptide Angiotensin Corticotropin-releasing factor Beta-endorphin