synaptic transmission Flashcards
what did the concept of chemically-activated channels arose from?
the study of synaptic transmission
in 1900 Ramon y Cajal noted what?
withtin a circuit, neurons are separated by physical gaps; such gaps impose the concept of a diffusible factor as the mediator of NT in CNS
in 1920 Dale and Loewi proved what?
that upon stimulation nerves release a diffusible substance (acetylcholine) that activates a contractile substance in the heart muscle
in 1944 Eccles established what?
that a synpatic transmission in the CNS was a chemical process as well
in 1959 Curtis, Phillis, Watkins demonstrated what?
in CNS excitatory action of glutamate, depressive actions of glycine and GABA
what is a synapse technically defined as?
any junction where one neuron can communicate with another neuron of cell type
the flow of information is typically?
one direction
where does an electrical synapse occur at?
gap junction
what is a gap junction?
membranes separated by ~3nm, brought together by intermemebrane proteins called connexins
what is a connexin?
they form channels that can pass ions from one to another. many connexins make up a gap junction
how many neurotransmitters do neurons have?
only 1
what are fast excitatory synapses?
they are more likely to fire an action potential
they activate ion channels
pass cations, Na+, K+, Ca2+
glutamate is the main, sometimes aspartate, and acetylcholine in some cases (especially at neurotransmitter junction)
what are fast inhibitory synapses?
activate ion channels
pass anions Cl-
GABA, glycine, acetylcholine in some cases
what are slow synapses?
activate GPCRs
can be excitatory or inhibitory
what are chemical synpases generally used for?
the transport of ions in order to generate electrical current
once an axon potential reaches the axon what does it instruct the synaptic vessels to do?
to be released into the synaptic space
what are the steps in a chemical synapse?
synthesize and package neurotransmitter
releasing vesicles from the axon terminal
production of postsynaptic response (ligand gated and GPCRs)
removing neurotransmitter from the synaptic cleft
where can neurotransmitters come from?
food as amino acids
what are amino acids
building blocks for all proteins and are all therefore ubiquitous in all cell types (glutamate and glycine)
describe neurotransmitter synthesis and packaging
enzymes are transported to the axon terminal that can synthesize GABA and amine neurotransmitters
transporter proteins in the membrane of the synaptic vesicle allow entry of neurotransmitter (only one type of transporter protein made in a neuron usually)
peptides are synthesized in the rough ER and sent to the axon terminal in secretory vesicles via anterograde transport alone microtubules
describe synaptic transmission
action potential at the axon terminal activates voltage gated Ca2+ channels
Ca2+ ions cause vesicles to fuse with cell membrane (exocytosis)
exocytosis occurs in 2 steps and is dependent on a calss of proteins called SNAREs
what are the 2 steps of exocytosis?
- dock the synaptic vesicle at the presynaptic membrane so it can fuse immediately
- initiate exocytosis
what does Ca almost always do?
move into the neuron
number 1-6 in the order they occur:
1. once action potential reaches the axon terminal voltage gated Ca channels open and Ca moves in
2. Ca activated synaptotagmic which “tag you’re it” now the SNAREs can bind
3.synaptic vesicle just been made getting sent down to axon terminal
4. neurotransmitters released
5. synaptic vesicle reaches axon terminal, attaches SNAREs proteins
6. initiates exocytosis of synaptic vesicle
3, 5, 1, 2, 6, 4
what does synaptobrevin do?
acts like a rope “docking the boat” traps it and keeps it close
how are neurotransmitters removed and cleared for future signaling?
diffusion out of the synapse to extrasynaptic spaces
reuptake by membrane proteins that transport neurotransmitters into the presynaptic cell
enzymatic degradation of neurotransmitter in the synaptic cleft
what do ion channels do?
act as “gates” in an otherwise impermeable membrane “fence”
what stimuli can “gate” ion channels?
ligand gated
voltage gated
stretch and heat gated
T/F: ion channels do not indiscriminately pass all ions down their concentration gradient
true
ion channels either exclusively pass anions or cations
some ion channels are selective and can only pass one type of ion
what are the primary receptors that initiate a biochemical cascade?
GPCRs
what is the goal of GPCRs?
to alter the function of a target protein
How do GCPRs work?
the receptors are coupled with the response by a GTP-binding protein (G-protein)
at rest, a GPCR is bound to a G-protein, which itself is bound to GDP
binding of a signaling molecule to the GPCR causes GDP to unbind from the G-protein and GTP to bind
the G-protein unbinds from the GPCR
the activated G-protein can then signal to other enzymes to activate them
how are GPCRs functionally diverse, but structurally similar?
seven transmembrane helices
G-proteins contain 3 subunits
alpha subunit loosely with membrane and connects with target protein
beta and gamma subunits more closely associated with membrane and can alter ion channel activity
in addition to a stimulus and receptor, there must also be a what?
a target molecule inside the cell that can carry out the cellular response
what is the process by which a receptor signals to the target molecule called?
signal transduction
what are second messengers?
any molecule after receptor has been activated that carries out the orders on the inside of the cell
what does signal transduction typically involve?
signaling between multiple molecules
what does signal transduction allow for?
signal amplification (one molecule can signal to multiple other molecules)
what is the most common intracellular messenger in neurons?
Ca2+
what can Ca2+ do?
directly bind to a number of proteins, altering their function. intracellular concentration can rise by Ca2+ permeable ion channels or from the ER, release from the ER is through IP3 receptors
what is cyclic AMP (cAMP)?
a derivative of ATP. gets produced by adenylyl cyclase converting ATP into cAMP
signals to the protein kinase PKA
what are DAG and IP3?
membrane lipids that can be converted into second messengers. they get generated when PIP2 gets split by phopholipase C into DAG and IP3. DAG remains in the membrane and can activate protein kinase C (PKC). IP3 can release Ca2+ from intracellular stores
what is a major way by which biomechanical cascades exert their effect?
by the post-translational modification phosphorylation
what are kinases?
enzymes that add phosphate groups to proteins
what are phosphates?
enzymes that remove phosphate groups from proteins
what are the targets of kinases and phosphates?
other enzymes, neurotransmitter receptors and ion channels
what regulates activity of kinases and phosphates?
Ca2+, cAMP, DAG, growth factors etc
what are some major kinases?
PKA, CaMKII, PKC, PTK
what are some major phosphates?
PP1, PP2A, and PP2B
what is nuclear signaling?
prolonged changes to neuronal function can be initiated by changing the expression patterns of certain proteins (alter RNA transcription -> alter protein transcription -> higher/lower levels of proteins)
how long does nuclear signaling take?
30-60 minutes
how long does it take to reverse nuclear signaling?
days to reverse
what is CREB?
the protein in the nucleus that determines transcriptional activity. CREB is unphosphorylated. activation of signaling pathways can lead to CREB phosphorylation which increases transcription. PKA phosphorylates CREB, Ca2+ activates CaMKII which phosphorylates CREB
