NT Systems (finished) Flashcards
Expose you to the major neurotransmitter systems (neurons) in the brain Provide the basis for understanding subsequent lectures on specific agents utilized to treat specific diseases Allow for understanding of how each neuronal system could be involved in various disease states
Neurons contain two general types of channels
Voltage-gated: -Na -Ca Ligand-gated: -Glutamate, GABA, 5 HT
Ligand-gated channels
Open briefly (tens of milliseconds)
Account for fast action potentials
An example is glutamate receptors
Metabatropic receptors
Receptor interacts with a GTP-binding protein
Modulates voltage gated channels
Typically enhances K or inhibits Ca channels
Typically inhibitory
Elevating Ca is generally stimulatory or inhibitory?
Stimulatory
chemical transmission
Presynaptic membrane depolarization activates Ca channels
Ca entry into presynaptic neuron promotes docking of vesicles with plasma membrane
Releases vesicle contents
Chemical transmitter diffuses across synapse
Chemical transmitter binds to its receptor, briefly changing membrane potential
Process takes 0.5 msec per synapse
Mechanism of Action of Drugs
Action potential (lidocaine blocks Na channels)
Synthesis of neurotransmitter (DOPA to increase dopamine)
Storage of neurotransmitter (reserpine depletes norepinephrine)
Metabolism of neurotransmitter (Monamine oxidase inhibitors prevent monoamine metabolism)
Release of neurotransmitter (methamphetamine)
Uptake of neurotransmitter (Cocaine prevents dopamine uptake into nerve)
Degradation of neurotransmitter (Anticholinesterase prevents acetylcholine degradation)
Receptor interaction with neurotransmitter (Either agonists or antagonists can be used for a variety of applications)
Ion conductance (lots of methods to influence this)
Hierarchical and diffuse systems
Hierarchical systems
These are systems aligned in order almost linearly
Examples are sensory perception and motor control
Diffuse systems
These systems are not highly ordered and effect numerous regions of the brain via diffusion of neurotransmitter
Examples are monoaminergic containing neurons
Norepinephrine, dopamine, 5 Hydroxytryptamine
Glutamate
Glutamate is a stimulatory neurotransmitter (postsynaptically)
Acts to increase cations within recipient neurons
Three types of receptors
-AMPA (alpha-amino-3-hydroxy-5-methylisoxazolo-4-proprionic acid) (Na & K)
-NMDA (N-methyl-D-Aspartate) (Ca, Na and K)
Needs depolarized membrane potential to work
Involved in memory
-Kainic acid (Na & K)
Involved in motor pathways
Presynaptically, Glutamate can inhibit neurotransmission (metabotropic)
Neurotransmitters associated with Hierarchical Systems
GABA (Gamma- aminobutyric acid)
Inhibitory neurotransmitter
GABAA is a Cl channel
When Cl- channels are activated, the cell is hyperpolarized
GABAB is a metabatropic receptor
Either augment K or inhibit Ca channels
Inhibits adenylyl cyclase
A number of agents act to enhance the actions of GABA receptors
Benzodiazepines activate GABA receptors to cause sedation
A GABA receptor agonist (baclofen) is a muscle relaxant
What do you think happens if you take away the influence of GABA??? Headless Chicken
Glycine
Inhibitory neurotransmitter of spinal cord & brainstem
Receptor is permable to Cl-
That means it will do what to Membrane potential????
Strychnine is an example of an antagonist of the Glycine receptor
If it’s blocking an inhibition of motor activity, what activity do you think it causes ???
Acetylcholine
Acts on two general classes of receptor Nicotinic Sodium channel causing depolarization Muscarinic Metabotropic receptor reducing cAMP or increasing Ca Also increases Potassium permeability Involved in cognitive functions & memory How might you improve memory?
Dopamine
Acts on a number of receptors but can primarily be divided into:
D1 receptors
Couples to Gs protein to stimulate cAMP production
Probably associated with Tourrette’s Syndrome
D2 receptors
Couples to Gi protein to suppress cAMP production
Particularly important in substantia nigra to neostriatum projections
Dopamine in this region is depleted in Parkinsons Disease
Acts to suppress GABA release
Inhibits an inhibition of movement
Present in ventral tegmental to limbic structure projections
Has a slow inhibitory action
Antipsychotics frequently work to antagonize these receptors
Some antidepressants prevent dopamine uptake into neuron, thereby increasing receptor stimulation
Norepinephrine
High concentration of cell bodies in locus coeruleus (name means “blue spot”)
Acts via alpha2 receptors to increase potassium conductance
What does this do to membrane potential?
So is it stimulatory or inhibitory?
Alpha2 receptor agonists can be used as muscle spasmolytics
Other receptors (Alpha1 and beta) are involved with attention and arousal
Serotonin
Abundantly present in raphe or midline region of Pons
5HT3 receptor is ionotropic and excitatory
conducts cations
5HT2a is metabotropic
Agents blocking this receptor improve schizophrenia and bipolar disorder
Serotonin reuptake inhibitors increase the amount of serotonin interacting with this receptor
Creates an anti-depressant effect
Opioids
Suppress pain by interacting with a µ receptor
Decrease Calcium and cAMP
Also interact with delta and kappa receptors
Works in spinal cord
