Neurotransmitters and Excitotoxicity Flashcards
Inhibitory post-synaptic potentials
Small, localized hyperpolarizations almost always associated with chloride entry into the cells. The move the cell further from threshold and make AP less likely
Excitatory post synaptic potentials
Small, localized depolarizations commonly produced by entrance of sodium and/or calcium into the cell.
Summations
Occurs in the post synaptic cell when multiple IPSPs and EPSPs are elicited by different synapses or by repetitive action of the same synapse (temporal or spatial summation). If there are more IPSPs than EPSPs, the cell is inhibited and no AP occurs and visa versa
Gs metabotropic receptors
Proteins activate adenylate cyclase which leads to increased production of cAMP from ATP. cAMP activates PKA which phosphorylates downstream targets, either increasing or decreasing activity.
Gq metabotropic receptors
Activate phospholipase C, which then creats IP3 (PIP) and DAG
IP3/PIP activates calcium release, or it can work with DAG to activate PKC which will phosphorylate downstream targets.
Fast transport
Usually associated with synaptic vesicles containing peptide neurotransmitters which cannot be made or recycled at the pre-synaptic terminal.
Slow transport
Used for structural or other components not needed quickly such as mitochondria and synaptobrevin. Also used for protein/chemicals needed at other locations of neurons such as voltage-gated sodium channels which are used at nodes of ranvier, not the pre-synaptic terminal. Fast route is direct route to pre synaptic terminal
Excitotoxicity
When something blocks the delivery of oxygen or glucose to the brain, the neurons in the brain will start to depolarize as the ATP levels fall. There is excess activation which allows huge amounts of calcium to enter the post-synaptic cell. This excess calcium leads to activation of enzymes that lead to the production of nitric oxide, damaging the membranes and even triggering apoptosis in the cortex
Catecholamines
Includes dopamine, epinephrine, norepinephrine
Synthesized from tyrosine by tyrosine hydroxylase
For epinephrine to be synthesized, its precursor norepinephrine must be released from the vesicle it was made in. Phenylethanolamine-N-methyl-transferase PNMT is then able to convert norepinephrine to epinephrine
4 major pathways using dopamine
Substantia niagra- important in controlling voluntary motion, related to Parkinson’s
Mesolimbic- this pathway runs from the ventral tegmental area to the nucleus accumbens. Related to pleasure/reward system
Mesocortical- runs from ventral tegmental area to the cortex, especially the frontal cortex. Crucial to attention and higher levels of consciousness. Damage is associated with alterations in cognition/consciousness. Dysfunction linked to schizophrenia
Tuberinfundibular- runs from hypothalamus to anterior pituitary. Suppresses prolactins release from pituitary
Catecholamine receptors
Alpha-1 uses Gq
Alpha-2 uses Gi
Betas use Gs
Dopamine binds its own receptors D1, D2 etc.. and activate Gi proteins
Location of serotonergic neurons in CNS
One cluster of neurons in the brain stem known as the midline raphe nuclei
Serotonin destruction
Like catecholamines, serotonin is also destroyed by monamine oxidase
Location of histaminergic neurons
Very specific nucleus of the posterior hypothalamus known as the tuberomammillary body
Histamine destruction
Diamine oxidase degrades histamine
Locations of Ach as neurotransmitter in PNS
NMJ Autonomic preganglionic synapses Parasympathetic post-ganglionic fibers Sympathetic post-ganglionic fibers for sweat glands/muscle vasodilators Amacrine cells in retina
Locations of Ach as neurotransmitter in CNS
Striatum (motor control)
Brainstem arousal system
-the circuit involving the peduculopontine tegmental and laterodorsal pontine nuclei
-also the basal forebrain arousal system (ventral output from reticular activating system)
-producing arousal (non-specific increase in cortical activity produced by sensory info arriving at brainstem arousal systems)
Synthesis of acetylcholine done by ___, then transferred into vesicle by
Caholine acetyltransferase
Vesicular acetycholine transporter protein VAchT
Ach destruction
True cholinesterase on post synaptic cell membrane
Pseudocholinesterase found in blood and acts on other choline esters
Broken into acetate and choline, choline is taken up by presynaptic cell for recycling
Atropine
Blocks muscarinic cholinergic receptors
M1-M5 location and effect
M1- post ganglionic neurons of ANS, broad distribution in CNS. Gq protein leads to increased IP3 and DAG
M2- cardiac- Gi protein decreases cAMP leading to increased K+ conductance
M3- smooth muscle of bronchi and vasculature- Gq leads to increased IP3 and DAG
M4- presynaptic autoreceptors controlling Ach release; striatum of basal ganglia for motor control- Gi leads to decreased adenylate cyclase
M5- cerebral vasculature and basal ganglia dopaminergic neurons for motor control- Gq protein leads to increased IP3 and DAG
Nicotinic receptor
5 subunits, each coded by different gene Alpha, beta, gamma, sigma, epsilon May be heteromeric or homomeric Fetal- 2 alpha, beta, gamma, sigma Adult- 2 slpha, beta, gamma, epsilon Change in subunit decreases the open time of the channel but increases sodium entry
Excitatory neurotransmitters in CNS
Glutamate, aspartate, maybe taurine
GABA- derivation, removal, metabolism of GABA
Major inhibitory neurotransmitter in brain
Found all over CNS
Derived from glutamate by glutamate decarboxylase (GAD)
Removed from synapse via GAT (GABA transporter)
GAT1- on presynaptic terminal (repackaged into vesicle as is)
GAT2- on glial cells like astrocytes (converted to glutamine then released to be taken back up by presynaptic cell and recycled back into GABA)
GABA, Stiff-person and diabetes mellitus diseases
Stiff-person: Increased muscle rigidity and muscle spasms associated with decreasing GABA content
Pancreatic beta cells produce and release GABA, so GAD is found in the pancreatic islet. Antibodies to GAD are most common identified type in Type I diabetes
GABA(a) receptor
Ionotropic
Related to nicotinic Ach receptor
5 subunits alpha, beta, gamma, delta, epsilon
Chloride chanel causing influx of chloride - IPSP
Benzodiazepine binding site on alpha subunit potentiates increase in chloride conductance
Also metabolites of progesterone and deoxycorticosterone potentiate its effects and produce drowsiness
