Neuromuscular Physiopathology 1 Week 4

Electrical synapse

involves free transmission of ions between two cells connected by a gap junction

Connexons

transmembrane proteins that connect electrical synapses

Chemical synapse

the presynaptic neuron releases a neurotransmitter onto a postsynaptic neuron

What type of ion channel is found in high concentrations on presynaptic membranes?

Voltage-gated Calcium channels

FPM

fusion protein macromolecule, a matching pair of them will occur on the presynaptic membrane and a neurotransmitter vesicle, allowing the vesicle to split "Synaptophysin"

Clathrin

assists with inward movement of vesicle membranes

Dynamin

pinches the neck of emerging vesicles to complete its separation

Calmodulin

expels the vesicle content into the synaptic cleft

Ionotropic receptors

ion channels where neurotransmitters bind directly on receptor to open them (e.g. glutamate receptors) (ion channels)

Metabotropic receptors

neurotransmitters make a linkage by use of a membrane protein from the G-protein family (e.g. GABA receptor)

T or F: Metabotropic receptors act faster than Ionotropic receptors

False (ionotropic acts faster)

Binding component

protrudes outward from the membrane into the synaptic cleft

Ionophore component

passes all the way through the postsynaptic membrane to the postsynaptic neuron

Second messenger

an activator that is not an ion channel, but is a molecule that activates one or more substance in the postsynaptic neuron

T or F: Second messengers cause rapid effects in the activity of neurons

False (they cause prolonged changes in the activity of neurons)

What percent of second messenger activations are transducer with G-protein coupled receptors

75%

Criteria for a neurotransmitter

Must be present in a neuron

Substances must be released following depolarization

Postsynaptic membrane must contain specific receptors for it

Isolated substance must exert the same effect when applied to a target neuron

Antagonist molecules must block the effect

Physiological mode of termination of the transmitter effect must be identified

Small-molecule neurotransmitters

rapidly acting, cause most acute responses of the nervous system

Neuropeptides

large, slow acting molecules that cause more prolonged actions e.g. long term opening or closure of ion channels

Hormones

Slow and long lasting effects that act at distant locations (carried by blood)

Neuromodulators

Modify the release of NTs

Peptides have neuromodulatory actions

E.g. adenosine modulates presynaptic dopamine release

Biological Amine NTs

Acetylcholine

Monoamines

Catecholamines (dopamine, NE, epinephrine)

Serotonin

Histamine

Amino Acid NTs

Glutamate

Y-aminobutyric acid (GABA)

Glycine

Hypothalamic-releasing hormones

Thyrotropin-releasing hormone

luteinizing hormone-releasing hormone

Somatostatin

Pituitary peptides

Adrenocorticotropic hormone (ACTH)

B-endorphin

Prolactin

Luteinizing hormones

Thyrotropin

Oxytocin

Glutamate

The most prevalent excitatory transmitter in the brain

T or F: All neurons projecting into the white matter from the cerebtral cortex are excitatory and use glutamate as a transmitter

True

Y-aminobutyric acid (GABA)

Principal inhibitory neurotransmitter in the brain

Glycine

An important inhibitory NT of the spinal cord

Main function is to provide tonic negative feedback onto motor neurons

Inhibited by tetanus toxin

Acetylcholine (ACh)

Claimed to be the first discovered NT

Degeneration consistently associated with alzheimer's disease

Used for communication in all neuromuscular junctions

Ligand-gated nicotinic receptors

found at neuromuscular junctions in all autonomic ganglia and the CNS, activation by ACh causes depolarization of target neuron

G-protein gated muscarinic receptors

found in the temporal lobe of the brain, autonomic ganglia, cardiac muscle fibers, smooth muscle of intestines and bladder, and sweat glands

Excitatory subgroups

M1, M3, M5

Inhibitory subgroups

M2, M4

Dopamine

motivational component of reward behavior

Of clinical significance in parkinson's, drug addiction, and schizophrenia

Substantia nigra

primary source of dopamine

Ventral part of the tegmentum

projects dopaminergic neurons into the forebrain, creates the dopamine rush of drug addiction

T or F: All Dopamine receptors are G-protein coupled

True

Norepinephrine

released from postganglionic sympathetic neurons and is concentrated in the Cerulean nucleus

T or F: All norepinephrine receptors are nicotinic

False (they are all G-protein gated)

Serotonin

The most documented NT

Depletion is associated with depression

Fifteen groups have been identified

Receptor subtypes are ionotropic and metabotropic

T or F: All neuropeptide receptors are G-protein coupled

True

Agonist

something that mimics or enhances the activity of an NT

Cocaine

Catecholamine agonist

Blocks reuptake of catecholamines

Benzodiazepines

GABA agonist

Binds to GABA molecule and increases its binding activity

Atropine

ACh antagonist

Binds and blocks muscarinic receptors, a high dose can disrupt memory

Curare

ACh antagonist

Binds and blocks nicotinic receptors at the NMJ, causes paralysis