Neurochemistry Flashcards
Na+ Channel Activation & Inactivation
-Tetrodotoxin (TTX – puffer fish) and saxitoxin (STX / paralytic shell fish toxin – PTX) block voltage-gated Na+ channels
-Batrachotoxin (BTX – frog) forces
Na+ channels to stay open
K+ Channel Inactivation
-Agitoxin (scorpion) and betabungarotoxin (snake) block voltagegated K+ channels
Multiple Sclerosis
-degenerative disease that attacks the central nervous system
-WBCs attack neurons
-affect fatty tissues (myelin) around the nerve fibers in brain, spinal cord
Synapse
-The “connection” between an axon terminal of one cell (pre-synaptic cell) and the dendrite or soma of another cell (post-synaptic cell) is called a synapse.
-These neurons are not in physical contact – there is a small space in between them. This small space between the two neurons is called the synaptic cleft.
When one neuron (pre-synaptic) generates an action potential, the neuron (post-synaptic)
with which it is connected exhibit:
-Inhibitory Post-Synaptic Potential (IPSP)
-Excitatory Post-Synaptic Potential (EPSP) - summation of EPSPs = action potential
Action Potentials cause neurotransmitter release
-As a result of an action potential, voltage-gated Ca+2 channels at the axon terminal (bouton) open and Ca+2 enters the cell
Ca+2 causes synaptic vesicles to fuse with the presynaptic membrane and release neurotransmitter into the synaptic cleft, a process known as exocytosis
Neurotransmitters
-The chemical released from the pre-synaptic axon terminal that serves as the basis of communication between neurons
-Many different chemicals act as neurotransmitters in brain:
–Glutamate, GABA, dopamine, serotonin, norepinephrine, acetylcholine
-Each neuron releases one (or maybe two or three!) neurotransmitters; different neurons release different neurotransmitters
-Each neurotransmitter can trigger a different effect on the post-synaptic cell
Where are neurotransmitters made and transported?
-Some neurotransmitters are made in the soma of neurons and then transported to the axon terminals by motor-proteins
-Some neurotransmitters are made
in the soma as well as in the axon
terminal
Neurotransmitter production
-Neurons must synthesize their neurotransmitter and move it into vesicles
-A specific enzyme (protein) is involved in producing each neurotransmitter
-Often, that enzyme converts an amino acid we derive from our diet into a neurotransmitter
Steps from release to inactivation: The Pre-Synaptic Side
- The action potential is propagated over the presynaptic membrane
- Depolarization of the presynaptic terminal leads to influx of Ca+2
- Ca+2 promotes exocytosis, the fusion of vesicles with the presynaptic membrane, which releases transmitter into the cleft
- The binding of neurotransmitter to receptor molecules in the post-synaptic membrane opens channels. This permits ion flow and initiating an excitatory or inhibitory post-synaptic potential
- Excitatory or Inhibitory post-synaptic potentials spread over dendrites and cell body to the axon hillock
6a. Enzyme present in the extracellular space breaks down excess neurotransmitter
6b. Reuptake of neurotransmitter slows synaptic action and recycles neurotransmitter for subsequent transmission
- Transmitter binds to autoreceptors in the
presynaptic membrane
Post-synaptic Density
-The post-synaptic zone is comprised of
protein complexes that include the targets
of the released neurotransmitter-receptors
-These receptors initiate a cascade of
intracellular events by activating particular
molecules
-These molecules then further activate ion
channels promoting a shift in membrane potential towards a less negative voltage/potential
Receptors
-ionotropic receptors
-metabotropic receptors
Ionotropic receptors
-allow ions to flow through when activated
-Same as ligand-gated ion channels– chemically triggered
-Form cation (Na+, K+, Ca+2) or anion (Cl-) channels
-Neurotransmitter binding to channel results in opening of the channel
-Thus, activation of the receptor can result in change in flow of electrically charged ions across the membrane – fast responsive
Metabotropic receptors
-coupled to g-protein which then activates ion channels
-Single transmembrane proteins
-Neurotransmitter binds to the extracellular domain
-Coupled to GTP-binding (G) proteins which in turn couple to other enzymes or channels
-Thus, activation of the receptor can result in slower biochemical changes within the cell or alterations of membrane polarization
Endogenous Ligand
a naturally occurring molecule, such as, a
neurotransmitter, that binds to the receptor.
-An endogenous ligand usually activates its
cognate receptor and is therefore classified
as an agonist
