Anatomy 2 exam 1 Flashcards
- Compare and contrast electrical and chemical synapses;
electrical
- Channels physically connect two neurons
- Ions (electric currents) flow between neurons
- Gap junctions
-Fast and two-way traffic
Chemical
- Gap between two neurons
- Chemical released from one neuron, diffuses across gap
- Slow, and one-way from pre- to post
chemical transmission steps
Chemical transmission
- Multiple steps are required to release transmitter chemicals and for them to act on postsynaptic receptors, resulting in a time delay
- Directional - presynaptic to postsynaptic terminals.
- Can change signs by release of inhibitory transmitter
- Can be modulated as it has many steps at the presynaptic and postsynaptic sites.
small and big molecule transmitters
- Small clear vesicles (50 nm)
- Synthesized in pre-synaptic terminal
-Synthesizing enzymes transported to terminal
•Released in response to single action potential
Large, dense-core vesicles
90-250 nm diameter
Synthesized in soma
Transported to pre-synaptic terminal
Released in response to burst or repetitive action potentials
Role of calcium and exocytosis in neurotransmitter release;
vesicles are released by exocytosis.
what causes the depolarization
opening of calcium channels
what are postsynaptic potential and name the two types
Postsynaptic potentials are changes in the membrane potential of the postsynaptic terminal of a chemical synapse
- Graded potentials
- Strength determined by:
- Amount of neurotransmitter released
- Time the neurotransmitter is in the area
• Two Types of postsynaptic potentials
1.EPSP—excitatory postsynapticpotentials
2.IPSP—inhibitory postsynapticpotentials
- Describe what ion movement can cause EPSP or IPSP;
Whether a postsynaptic response is an EPSP or an IPSP depends on the type of channel that is coupled to the receptor, and on the concentration of permeant ions inside and outside the cell. … When these glutamate receptors are activated, both Na+ and K+ flow across the postsynaptic membrane.
-NA+ and K+
An IPSP is a local
hyperpolarization of the
postsynaptic membrane
and drives the neuron
away from AP threshold.
Neurotransmitter binding
opens K+ or Cl– channels.
Can EPSP induce an action potential?
- EPSPs can summate to reach threshold
- IPSPs can also summate with EPSPs, canceling each other out
Temporal summation
One or more presynaptic neurons transmit impulses in rapid-fire order (ie, in time)(same synapse, different times)
Tep excitatory stimuli close in time cause ESPS’s that add together
spactial summation?
Postsynaptic neuron is stimulated by a large number ofterminals (ie, in space) at the same time (different synapses, same time)
- Two or more synapse involved
Spacing has to be close to each other
-Change in membrane potential can cancel each other out.
neurotransmitters route (3 steps)
- Synthesis
- Precursors
- Rate limiting steps
- Location (Cell types) - Inactivation
- Post-synaptic receptors
- Structure
Subtypes
two receptor types include
Ionotropic receptor = ligand-gated
ion channels (fast)
Metabotropic receptor=
G Protein- Coupled Receptor (slow)
neurotransmitter receptors
inotropic and metatropic
- Ionotropic –
§Electrical response to neurotransmitter binding
§Large, 4-5 subunit protein forms channel
§Impermeable in the absence of transmitter
§Rapid onset, rapidly reversible
- Metabotropic –
§G protein coupled receptor (GPCR)
§Single polypeptide receptor
Slow onset, long duration
acetycholine synthesis
- Synthesis
- Acetyl from acetyl coA is transferred to choline by choline acetyl transferase (ChAT)
qChAT is rate limiting step
-Acetyl coA precursor
**Derived from pyruvate (glucose metabolism)
**Must exit mitochondria to gain access to ChAT
-High affinity Na+/Choline transporter moves choline into neuron
- Describe inhibitory amino acids and their receptors (GABA and glycine);
•Excitatory: Glutamate and Aspartate
•Inhibitory: g amino butyric acid (GABA) and glycine
•Major neurotransmitters in CNS
Glutamate synthesis and inactivation
Inactivation
Glial transporter takes out glutamate for it to bind to the glutamate receptors
Glutamate taken up by astroglial cells is converted to glutamine.
it allows glutamate to be inactivated by glial cells and transported back to neurons in an inactive (non-toxic) form.
Synthesized
glutamategic neurons
•Ubiquitous, excitatory transmitter
§Pyramidal neurons of cortex and hippocampus
§Granule cells of cerebellum
§Thalamus
•Difficult to distinguish glutamate from aspartate
glutamate receptor types
iGluRs and mGluRs; NMDA receptors, and AMPA receptors);
Ion channel associated : inotropic (iGluR)
NMDA–> AMPA–> KAINATE [THESE ARE FAST: EXCITATORY]
G protein-coupled : Metabolic (mGLuR)
group 1–> Group 2–> group 3
group 1 [slow excitatory] [Gq post-synaptic]
grouop 2 and 3 [slow inhibitory] [Gi pre-synaptic]
Describe glutamate receptor types (iGluRs and mGluRs; NMDA receptors, and AMPA receptors);
- Glycine is co-agonist
- Magnesium blocks pore unless depolarized
- Calcium permeates channel
Excitatotoxicity is caused by
- Caused by abnormally high levels of glutamate
- Dendrites of target neurons are swollen
- Due to calcium flood
- Effect blocked by glutamate antagonists - Observed after ischemia, e.g. due to stroke
- Clinical trials using glutamate antagonists were disappointing
- Treatment may occur too late
- Describe inhibitory amino acids and their receptors (GABA and glycine);
- Glutamic acid decarboxylase (GAD) forms GABA from glutamate
- GAD uses pyridoxal phosphate as co-enzyme
- Pyridoxal Phosphate is active form vitamin B6
Ionotropic GABA receptors
- Chloride permeable channels
- Chloride influx produces IPSP
- Stop firing
- Decrease firing rate
GABAA receptors are
GABAB receptors are
GABAA receptors are ionotropic;
GABAB receptors are metabotropic.
GABAA receptors are ligand-gated ion channels (also known as ionotropic receptors); whereas GABAB receptors are G protein-coupled receptors, also called metabotropic receptors.
TO KNOW
Ionotropic receptors are membrane-bound receptor proteins that respond to ligand binding by opening an ion channel and allowing ions to flow into the cell,
metaropic receptor use signal transduction mechanisms, often G proteins, to activate a series of intracellular events using second messenger chemicals.
Excitatory Actions of GABAA in developing Brain
- Developing brain has higher Na/K/Cl co-transporter
§Higher intracellular chloride
- Older brains have higher K/Cl co-transporters
§Lower intracellular chloride
Describe what transmitters are included in “Catecholamines” (what are they?);
•Molecule with Catechol nucleus
-Benzene Ring with 2 adjacent hydroxyl substitutions plus amine group
•Types
- Dopamine (DA)
- Epinephrine (Epi or Adrenaline)
- Norepinephrine (NE or Noradrenaline)
•Act as neurotransmitters in CNS, PNS and hormonal function
biogenic amines include
catecholamines—dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline)—and histamine and serotonin
Describe dopamine (chemistry and anatomy) and receptors;
Describe norepinephrine and epinephrine (precursor, synthesis process, and anatomy);
- Locus C(o)eruleus produces NE
- Wide and diffuse projection
- Role in
- attention
- Sleep-wake cycles
Epinephrine Neurons and their projections
- Brain: medullary epinephrine neurons
- Project to thalamus, hypothalamus, medulla - Periphery: adrenal medulla
- Part of adrenal gland
- Endocrine organ near kidneys
- Fight or Flight
catecholamine synthesis
•Precursor
[Tyrosine]
qGeneral large amino acid transporter; energy dependent mechanism to cross BBB
•Rate limiting step (1st step)
§Tyrosine Hydroxylase
§Converts tyrosine to DOPA
Describe dopamine (chemistry and anatomy) and receptors;
d1 receptor familty: cyclic AMP increase
d2 receptor family: cyclic AMP decrese, K+ increase, voltage-gated Ca2+ currents
Describe serotonin synthesis precursor and anatomy;
- Regulates sleep-wake cycles
- Implicated in migraine and psychiatricdisorders
-Only one ionotropic receptor
[•5-HT3]
[•Non-selective cation channel]
Describe serotonin synthesis precursor and anatomy
•Indoleamine (group name)
§Indole structure similar to LSD
•Precursor
§Tryptophan
•Rate limiting step
§Tryptophan hydroxylase
Describe the termination of catecholamines by re-uptake
- Serotonin Transporter (SERT)
§Transports it into pre-synaptic terminal for re-use
§Inhibited by Fluoxetine (Prozac)
- Loaded into vesicles by VMAT (vesicular monoamine transporter)
Describe the role of MAO in the metabolism of monoamines;
- Degradation
1. Monoamine oxidase (MAO) - After re-uptake
- In mitochondria
- An enzyme called monoamine oxidase is involved in removing the neurotransmitters norepinephrine, serotonin and dopamine from the brain.
2. Catechol-o-methyltransferase (COMT) - In cytoplasm
- inhinit breakdown catacholamines
3. Both are targets of anti-depressant drugs
