Neurophysiology and Neurochemistry Flashcards
1
Q
Ion Concentrations in neurons
A
A- (amino acid) ions are higher inside the cell
K+ (Potassium) ions higher inside the cell
Cl- (Chloride) ions higher outside the cell
Na+ (Sodium) ions higher outside the cell
2
Q
Electrochemical Equilibrium
A
exact balance between electrochemical forces
- potential charge across a membrane exactly offsets
the concentration gradient
no net flux across the membrane
none of the ions of physiological importance in a neuron are in electrochemical equilibrium
3
Q
GABA Distribution and Behavioural Functions
A
ubiquitous throughout CNS (central nervous system)
one of the most common neurotransmitters (NTs)
lack can result in convulsions/death
can treat seizures, anxiety, and insomnia
4
Q
Ionotropic (Pentamers) GABA Receptors
A
GABAa
GABAc
5
Q
Metabotropic GABA Receptors
A
GABAb
6
Q
Acetylcholine (ACh) Distribution and Function
A
Cholinergic system: neurons into midbrain, basal forebrain, frontal cortex and corpus callosum
Active in maintaining attention and waking EEG pattern
Plays role in memory (maintains neuronal excitability)
Death of cholinergic neurons related to Alzheimers
7
Q
ACh Biosynthesis and Inactivation
A
Acetyl CoA + Choline (from metabolism or diet) = ACh
Acetylcholinesterase breaks down ACh
Choline is taken by reuptake proteins in the presynaptic terminal buttons
8
Q
ACh Ionotropic (Pentamer) Receptors
A
Nicotinic receptors
- affected by Botox and some poison curare
9
Q
ACh Metabotropic Receptors
A
Muscarinic receptors (M1 through to M5)
- affect the function of the ANS (autonomic nervous
system)
10
Q
Serotonin (Indoleamine) Biosynthesis
A
Tryptophan (from diet) + Tryptophan hydroxide =
5-hydroxtryptophan
5-hydroxytryptophan + Aromatic L- amino acid decarboxylase = Serotonin
11
Q
Temporal Summation
A
summation of ions entering/exiting neuron in close time to one another
12
Q
7 Steps in Neurotransmitter Action
or
7 Points at which Drugs can Interfere
A
- Molecules synthesized
- Molecules stored in vesicles
- Molecules that leak from vesicles are destroyed by enzymes
- Action potential triggers vesicle fusing with membrane and NT release
- NT molecules bind with autoreceptors inhibiting further NT release
- Released molecules bind with postsynaptic receptors
- Released molecules are deactivated by reuptake or enzyme degradation
13
Q
Receptors
A
membrane proteins that are bound to and activated by neurotransmitters
14
Q
Antagonist
A
prevents autoreceptors from being turned off
prevents neurotransmitters from binding to autoreceptors
means more release of NTs
15
Q
Agonists
A
binds to autoreceptors, turning them off and blocking further NT release
16
Q
Heteroceptor
A
presynaptic receptors activated by NTs different than those released from the same axon terminal
17
Q
Ionotropic Receptors
A
ligand-gated channels
comprised of multiple protein subunits which form an ion channel pore
18
Q
G-protein Coupled Receptors
A
alpha splits from beta and theta upon activation
effector protein (in the CNS, enzyme) produces other molecules that can work as ligands on the ion channel
ion channel opens
19
Q
Second Messenger
A
can open ion channels (with longer effects)
alter operation of non-gated ion channels in a way that alters membrane potential or sensitivity
the other signalling molecules triggered by effector enzyme
20
Q
G-Protein Pathway
A
- NT
- Receptor
- G-protein
- Effector protein
- Second messenger
- Later effectors
- Target action
21
Q
Gs G-Protein
A
- NT (DA)
- Effector (Adennylyl Cyclase)
- 2nd Messenfer (cAMP- opens ion channels and activates Protein Kinase A)
- Kinase (PKA- increases neuronal excitability and metabolic rate, can translocate into nucleus and turn on Transcription Factors)
- Transcription Factors - increase protein synthesis (gene transcription)
22
Q
Gg G-Protein
A
- Effector Enzyme (Phospholipase C) produces 2 second messengers
2a. Diacylglycerol
3a. PKC
4a. Increase protein phosphorylation and activates Ca2+ binding proteins
2b. IP3
3b. Ca2+ release
4b. Increase protein phosphorylation and activateds Ca2+ binding proteins
23
Q
Gi G-Protein
A
- Adenylyl Cyclase deactivates
- Less cAMP
- Less activated PKA
- Overall metabolic decrease within neuron
24
Q
Amino Acids
A
Glutamate and GABA
25
Monoamines
indoleamines and/or catecholamines
26
Cathecholamines
Dopamine
Norepinephrine
Epinephrine
27
Indoleamines
Serotonin
28
Ionotropic Receptor Function
attached to ion channels
opens ion channel
closes when NT leaves binding site
Influx of ions alters local potential
29
Metabotropic Receptor Function
Separated from ion channels and other proteins
uses G-protein to activate ion channels and effector enzymes
effector enzymes engage a cascade of events that persist after the NT leaves the binding site
can affect local potentials but has other effects including enzyme regulation, gene expression and protein synthesis
30
Biosynthesis of Catecholamines
In cytoplasm: L-tyrosine + tyrosine hydroxylase= L-DOPA
In vesicle: L-DOPA + DOPA decarboxylase = dopamine
dopamine + dopamine beta-hydroxylase = norepinephrine
In cytoplasm (from leakage): norepinephrine + phenylethanolamin n-methyl transferase = epinephrine
31
Metabotropic Dopamine Receptors
D1 receptor family (D1 & D5)
| D2 receptor family (D2, D3, D4)
32
Termination of DA Transmission
Reuptake transporters
Monoamine Oxidase (MAO) or COMT
33
Dopamine Distribution and Function
Dopaminergic System and Nigrostriatal Pathways
- frontal cortex, basal ganglia, cerebellum, and through
body
motor behaviour (can develop Parkinson's Disease with low dopamine)
reward/pleasure
addictive drugs and behavioural addiction
defecits of attention and schizophrenia are associated with imbalance
34
NE and E Metabotropic Receptors
Metabotropic alpha and beta receptors
35
Reuptake of NE and E
involves MAO and COMT
36
NE distribution and function
Noradrenergic System around brain and cerebellum
maintains emotional tone
decreases with depression
increases with mania
decreased NE activity associated with ADHD and hyperactivity
37
E distribution
adrenaline
thalamus and hypothalamus
medullary epinephrine neurons
spinal cord
38
Serotonin Receptors
all receptors from 5-HT1 through 5-HT7 are metabotropic except 5-HT3
39
Serotonin Transmission Termination
via reuptake and MAO
40
Serotonin Distribution and Function
Serotenergic System
waking EEG pattern
changes related to OCD, tics, and schizophrenia
decreases related to depression
abnormalities in 5-HT neurons related to sleep apnea and SIDS
41
Neuropeptides
synthesized in the cell body
initiate effects by activating G Protein-coupled receptors
catabolized into inactive amino acid fragments by peptides on extracellular surface of the cell membrane
activity depends on their amino acid sequence
42
Glutamate Biosynthesis and Inactivation
synthesized inside the axom terminal from the A.A. glutamine via glutaminase enzyme then released in vesicles
removed via glial reuptake and terminal button reuptake transport proteins
glial cells convert glutamate back to glutamine
- synaptically inactive
- taken back up by pre-synaptic neurons and cycle
begins again
no net gain within the glutamate/glutamine cycle
43
Nitric Oxide Synthesis and Function
gas functioning as an NT
NO synthase converts L-arginine into NO
activates enzyme to form PKG
combines with Citrulline to have other effects
free diffusion across membranes
44
Difference between NO and other NTs
not stored in vesicles
doesn't bind to receptors
gaseous
free diffusion across membranes
45
Equilibrium Potential for Na+
| ENa+
+66mV
46
EK+
-84mV
47
ECl-
-75mV
48
ECa2+
+134mV
49
Features unique to electrically excitable cells
response to membrane depolarization
- action potential
wherease a non-excitable cell will simply return to its original resting potential
50
Action Potential
the electrical excitability of a neuron
a rapid transient reversal of membrane potential that will travel uninterrupted from hillock to terminal
51
Threshold Potential
depolarization of more than +20mV that will result in an action potential
52
Voltage-Gated Ion Channels
Open with a change in membrane potential
| found mainly on the axon and the hillock
53
Na+ Voltage-gated channels
have open, closed, and inactivated settings (closure of inactivation gate)
are triggered at +20mV of depolarization
54
K_ Voltage-Gated Channels
triggered at +30 mV (peak potential)
55
Action Potential in Terminal Buttons
alters voltage and Ca2+ voltage-gated channels will open
- Ca2+ is necessary to make the vesicles that fust with
the membrane and to open cell pore
56
Neuroglia
Astrocytes: blood-brain barrier
Microglia: immune function (phagocytes)
Oligodendrocytes: insulate CNS
Schwann cells: insulate PNS
57
Ligand-gated Ion Channels
1/2 of major receptor class on dendrites and soma
ion channel that only operates when the appropriate NT binds with receptor
- will then allow channel to open and selected ions to
enter
depending on the ion channel opened, the neuron will be brought closer to or further from the threshold
58
Post-Synaptic Potential
changes in membrane potential of the post-synaptic neuron
graded potentials with the function to activate or inhibit the action potential
some ions let in by ligand-gated or G-Protein coupled receptors travel to the axon hillock
these ions then impact the likelihood of the threshold potential being reached
59
Summation of Inputs
a neuron sums all changes in charge that are close in time and space
60
Spatial Summation
all signals coming in from different locations on the soma and dendrites are summed
61
Types of NTs
```
Amino Acids
Modified Amino Acids
Monoamines
Neuropeptides
Gases
```
62
Ionotropic Glutamate Receptors
NMDA
AMPA
Kainate
all of these produce EPSPs
63
Metabotropic Glutamate Receptors
m-Glu1 through 8
| G-protein coupled receptors
64
Criteria that define a Neurotransmitter
1) Synthesis
2) Release
3) Receptor Action
4) Inactivation
65
NT Synthesis
some NTs are transported from the nucleus to the terminal button, others are made from material imported into the terminal button then packaged into vesicles
66
NT Release
NTs are packaged into vesicles that fuse with the membrane of the terminal button to release them in response to an action potential
This process is known as exocytosis
67
NT Receptor Action
NT crosses synaptic cleft and binds to a receptor
68
NT Inactivation
the NT is either taken up by the terminal or adjacent cells (reuptake), or inactivated in the synaptic cleft
69
Information Flow through Neurons
1) Dendrites
2) Cell body
3) Axon
4) Terminal buttons/Axon terminals
70
Plasma Membrane
```
single membrane that contains transport and receptor proteins
phospholipid bilayer (hydrophilic phosphate heads, hydrophobic lipid tails)
selective permeability to maintain intracellular environment
```
71
Cytoskeleton
no membrane
made up of actin filaments, microfilaments, microtubules
maintains cell structure, helps move materials around cell and can (in some species) help move entire cells
72
Mitochondria
double membrane; inner layer contains enzymes for ATP production
contains enzymes that catalyze oxidation-reduction reactions and ATP synthesis
Produces ATP
73
Vacuoles
single layer membrane with transporters for select molecules
components vary: pigments, oils, carbohydrates, water, or toxins
function varies: coloration, storage of oils, carbohydrates, water, or toxins
74
Peroxisomes
single membrane with transports for select macromolecules
contains enzymes that catalyze oxidation reactions (catalase processes peroxide)
oxidation of fatty acids, ethanol, or other compounds
75
Lysosomes
single membrane with proton pumps
components: acid hydrolases (catalyze hydrolysis reactions)
digestion and recycling
76
Smooth Endoplasmic Reticulum
single membrane with enzymes for synthesizing phospholipids
network of branching sacs, with enzymes for lipid synthesis
lipid synthesis
77
Golgi Apparatus
single membrane with receptors for products of the rough ER
stack of flattened cisternae
protein processing (e.g. glycosylation)
78
Rough Endoplasmic Reticulum
single membrane with receptors for entry of select proteins
network of branching sacs and ribosomes associated
protein synthesis and processing
79
Ribosomes
no membrane
made of a complex of RNA and proteins
synthesizes proteins
80
Nucleus
double envelope membrane with openings called nuclear pores
made up of chromosomes, nucleolus and the nuclear lamina
Functions: genetic info, assembly of ribosomal subunits, structured support
81
Resting Membrane Potential
neurons have a means of generating constant voltage across their membranes at rest (typically between -40 and -90 mV, usually around -70mV)
82
Forces that direct solute movement
A) Concentration Gradient: diffusion until equal amount on both sides of the membrane
B) Voltage Gradient: flow down gradient until equal charge is reached on both sides of a membrane
83
Ionic Electrical Signalling
Ions move down their electrochemical gradient if possible
Ions are not equally distributed between intracellular and extracellular fluid because the phospholipid bilayer serves as a barrier
84
Always open Ion Channels
transmembrane protein allowing free-flow of specific ions across the phospholipid bilayer
85
Mechanically-gated ion channels
open depending on cell pressure (flaccid or turgid)
86
Hyperpolarization
increased difference in charge
| - e.g. from -70 mV to -90 mV (farther from zero)
87
Depolarization
decreasing the difference in charge between two sides of the membrane
- e.g. from -70 mV to -50mV
moving closer to zero than start point
88
Properties of Animal Cells
establishing resting membrane potential with dependence on ion gradients and ion permeability
89
Polarized
there is a difference in charge on either side of the membrane
90
Hyperpolarization Phase
-75 mV
happens because K+ ion channels take a moment to close after normal potential is hit again
91
Refractory Period
period during which it is impossible or difficult for another action potential to be initiated
92
Relative Refractory Period
period during which it is possible but difficult to initiate another action potential; the hyperpolarization period
this is because there is further to move to reach the threshold of -50 mV
93
Absolute Refractory Period
period during which it is impossible for another action potential to begin
can't open Na+ when it's already open (depolarization) or when the inactivation gate is in the way (repolarization)
94
Saltatory Conduction
signal moves more quickly because the axon is myelinated
- the Na+ ions can't escape until the next Node of
Ranvier
important in extremely long axons
95
Continuous Conduction
rate of propagation decreases on the unmyelinated axon because the electrical pattern must repeat over & over at every point on the axon
96
Unidirectional Propagation
siggnal repeats itself down the length of a neuron but does not move backwards
because previous sodium gates have inactivation gates
sodium enters cell and diffuses enough to trigger next gates in next section
- signal strength doesn't change because it's self
propagating
97
Synapse
gap between terminal buttons and dendrites of neurons
98
Pre-synaptic Neuron
usually transmits signal
axon terminal on synapse
99
Post-synaptic Neuron
dendrites on synapse
has NT receptors (receives signal)
100
Neurons
excitable cells that analyze and transmit information
made up of soma, dendrites, axon hillock, axon and axon terminals
may be myelinated
sends electrical messages
101
Excitatory Post-Synaptic Potentials
brings membrane potential closer to threshold
| e.g. Na+, Ca2+
102
Inhibitory Post-Synaptic Potentials
caused by hyperpolarizing stimuli
e.g. K+ or Cl-
further from threshold
103
Agonistic Effect
promotes/facilitates NT action
104
Antagonistic Effect
impairs/inhibits NT action
105
Axodendritic Synapse
gap between axon terminal & dendrites
106
Axosomatic Synapse
gap between axon terminal & soma
107
Autoreceptor
presynaptic receptor activated by NTs released from the same axon terminal
108
Axoaxonic Synapse
side neuron releases NTs that affect effectiveness of main neuron
109
Presynaptic Facilitation
if an NT in an axoaxonic situation promotes the release of the NT from the main neuron
110
Presynaptic Inhibition
if NT from side neuron in an axoaxonic situation prevents or decreases the release of the NT from the presynaptic neuron
111
Metabotropic Receptors
large individual proteins that traverse membrane multiple times
indirectly linked with ion channels on the plasma membrane via signal transduction mechanisms
e.g. G-protein coupled receptors
112
Kinases
enzymes that alter the functioning of other proteins
can activate transcription factors
long-lasting effects
113
Transcription Factors
can alter gene expression by binding to promoters and activating or repressing transcription of a gene
114
Modified Amino Acids
ACh (Acetylcholine)
115
Indoleamines
Serotonin
116
Neuropeptides
endorphins
117
Gases
Nitric Oxide
118
Glutamate Distribution and Behavioural Functions
Ubiquitous within the CNS
one of the most abundant NTs
affects learning, motor activity, pain sensitivity
119
GABA Biosynthesis and Inactivation
Glutamate converte to GABA by GAD and vitamin B6
GABA reuptake into presynaptic cell and into glial cells where it's converted back to glutamate then glutamine and the cycle starts over
