Lec 12: Electrical Signals II Flashcards
AP propagation aka
(conduction)
(AP propagation/conduction)
APs move…
down the axon from the point of origin (usually the Axon Hillock region)
(AP propagation/conduction)
The depolarization at one region will
spread passively to surrounding regions
(AP propagation/conduction)
- The magnitude of the initial depolarization is…
- This is known as…
- lower at sites distant from the initial site.
- “electrotonic spread” or “passive spread” and it’s distance is determined by the length (space) constant, Lambda
(AP propagation/conduction)
- Lambda =
- and is determined by: (2)
= the distance it takes for the voltage response to decay to 37% of its original magnitude
- ) Axon diameter
- ) Presence or absence of myelination
(AP propagation/conduction)
- Passive electrotonic spread of the depolarization is not
- The take home message is that
- AP conduction, but helps to explain it
- depolarizations spread passively to surrounding regions!
(AP propagation/conduction of an Unmyelinated Axon)
5 Steps:
- ) At the start, the membrane is completely polarized
- ) (Passive depolarization spreads) When the action potential is initiated, a region of the membrane depolarizes. The adjacent regions become depolarized
- ) When the adjacent region is depolarized to its threshold, an action potential starts there.
- ) Depolarization occurs due to the outward flow of K+ ions. The depolarization spreads forwards, triggering an action potential. (The AP may be able to travel in reverse?)
- ) Depolarization spreads forward, repeating the process
(In the 5th step of AP propagation/conduction of an Unmyelinated Axon)
- The AP does not…
- because it is…
- However, passive spread is important in…
- fade (decay) like the passive spread of depolarization
- regenerated (in an “all or none” fashion) at successive regions along the axon
- setting up the AP from one region to the next region
(Anatomy of myelinated axon)
- Made up of…
- Each sheath is…
- Acts to…
& this: (2) - Performed by: (2)
- The gaps between sheaths are the…
- Myelination allows for…
- Note that the ____ ____ __ ______ are present only at…
- Multiple intermittently spaced sheaths of membranes wrapped around the axon
- spaced evenly along the axon length.
- insulate
1. ) Increases resistance
2. ) Decreases capacitance
- ) Oligodendrocytes in CNS
- ) Schwann cells in PNS
- Nodes of Ranvier
- more rapid conduction velocities
- voltage-gated Na+ channels, the Node!
(AP propagation/conduction of an Myelinated Axon)
5 Steps:
- ) In myelinated neurons, an action potential is triggered at the axon hillock, just before the start of the myelin sheath. The depolarization then spreads along the axon.
- ) Due to myelination, the depolarization spreads passively to the next node
- ) The next node reaches its threshold, and a new action potential is generated
- ) The cycle is repeated, triggering an action potential at the next node
- ) The process continues.. resulting in Saltatory Conduction
(In the 2nd step of AP propagation/conduction of an Myelinated Axon)
- The depolarization passively spreads…
- because…
- The passive spread is sufficient to…
- further along the axon in a myelinated vs. an unmyelinated axon
- the insulating myelin sheath prevents current leakage and effectively increases the lambda.
- bring the next node to above threshold level allowing for the AP to “skip” from node to node
How is the electrical signal transmitted from cell to cell?
Synapses (located at the terminal branches of axon)
2 Types of Synapses:
- ) Electrical (cells are “electrically coupled”)
2. ) Chemical (uses a neurotransmitter)
All synapses have at least __ cells
& what are they?
- 2 cells:
- ) Presynaptic cell
- ) Postsynaptic cell
(with Synaptic cleft = space in between the 2 cells)
Synaptic cleft =
= space in between the 2 cells
(Electrical Synapse)
1.) Involves…
- ) Composed of…
- ) The channel (“hemichannel”) of each pore (connexon) is…
- ) Each pore is composed of…
- ) Depolarization (AP) in one cell will…
- ) Important in…
- ) Gap Junctions (minimal synaptic cleft, 3.5 nm)
- ) pores that connect the cytoplasm of one cell to the next
- ) matched with the channel of a pore on the adjacent cell
- ) 6 protein subunits known as a connexin
- ) spread to the next electrically coupled cell
- ) cardiac muscle and some CNS synapses
(Chemical Synapse)
1.) AP in presynaptic cell (neuron) initiates…
- ) Neurotransmitter (chemical ligand) diffuses…
- ) Upon binding, the receptor initiates…
- ) the release of neurotransmitter (from synaptic vesicles) into the synaptic cleft (at presynaptic membrane of terminal bulb).
- ) across the cleft and binds to a specific receptor on the postsynaptic cell membrane (neuron or effector organ) (#2 in diagram).
- ) an electrical event (depolarization or hyperpolarization) that begins at post synaptic membrane of the postsynaptic cell (could be a multistep process) (#3 & #4 in diagram).
4 Types Different Neurotransmitters Discussed:
- Each presynaptic cell has only…
- Thus that cell is always either…
- ) Acetylcholine
- ) Catecholamines
- ) Amino Acids & derivatives
- ) Neuropeptides
- one main neurotransmitter
- excitatory or inhibitory
Acetylcholine is important in…
excitatory or inhibitory?
- PNS
- (excitatory)
Catecholamines function as…
excitatory or inhibitory?
- adrenalin-related compounds
- excitatory or inhibitory responses
4 Types of Amino acids & derivatives (Neurotransmitters):
Where they function?
(excitatory or inhibitory?)
GABA: CNS (inhibitory)
Glycine: CNS (inhibitory)
Serotonin: CNS (excitatory)
Glutamate: CNS (excitatory
Neuropeptides are…
- with Hundreds of…
- Frequently…
Examples: (2)
- small peptides
- different molecules (have long lasting effects)
- coexist with other neurotransmitters
- Ex: endorphins, enkephalins
Neurotransmitter Steps: (8)
- ) An action potential arrives at the presynaptic terminal bulb, resulting in a transient depolarization
- ) Depolarization opens voltage-gated calcium channels, allowing calcium ions to rush into the terminal
- ) Increasing calcium in the terminal bulb induces the secretion of some neurosecretory vesicles.
- ) Prolonged stimulation mobilizes additional, reserve vesicles.
- ) Neurotransmitter diffused across the synaptic cleft to the receptors on the postsynaptic cell.
- ) Binding of neurotransmitter to the receptor alters its properties
- ) Channels open, letting ions flow into the postsynaptic cell. Depending on the ion, channel opening leads to either depolarization or hyperpolarization.
- ) If sufficient depolarization occurs, an action potential will result in the postsynaptic cell
(AP induced neurotransmitter release)
At presynaptic cell: (3)
- ) AP causes voltage-gated Ca2+ channels in the membrane to open at the terminal bulb
- ) Ca2+ diffuses into the cell and causes synaptic vesicles to fuse to the presynaptic membrane
- ) Neurotransmitter is released into the cleft
(AP induced neurotransmitter release)
At postsynaptic cell: (2)
1.) Neurotransmitter binds to its receptor
- ) Induces a change in membrane conductance
- Excitatory (EPSP – excitatory postsynaptic potential)
- Inhibitory (IPSP – inhibitory postsynaptic potential)
- EPSPs and IPSPs are graded potentials (not APs)
Mechanism of synaptic vesicle docking and fusion =
“Stimulus-secretion Coupling” Regulated Secretion
(Mechanism of synaptic vesicle docking and fusion) (“Stimulus-secretion Coupling” Regulated Secretion)
The synaptic vesicles…
fuse with the presynaptic membrane via Ca2+-induced exocytosis
3 main sets of vesicles are present in the terminal bulb:
Each vesicle is associated with…
- ) Undocked (far from the membrane)
- ) Docked (close to the membrane) – held by tethering proteins
- ) Docked and primed (close to the membrane and ready for release)
…several membrane bound proteins
Particularly important parts on the vesicle are: (2)
1.) v-SNARES (vesicle SNAP receptor):
Synaptobrevin (VAMP) (in this example)
2.) Synaptotagmin (the putative Ca2+ sensor)
(Vesicle Docking (tethering))
Priming involves the interactions of: (2)
- ) v-SNAREs (vesicle-SNAP Receptor)
2. ) t-SNARES (target-SNAP Receptors)
(Synaptic Vesicle Priming)
- Synaptic vesicles associate with…
- Examples of t-SNAREs include…
- Upon interaction of v-SNAREs and t-SNARES the vesicles are…
- v-SNAREs bind to…
- the pre-synaptic membrane via the v-SNAREs and the t-SNAREs (located at the presynaptic membrane).
- SNAP-25 and Syntaxin (SYX)
- “primed” for release
- t-SNAREs which positions the vesicle very close to the cell membrane
(Vesicle Docking, Priming & Fusion)
4 Steps:
- ) The proper vesicle is recognized and bound by particular membrane-anchored tethering proteins
- ) A Rab GTPase bound to the incoming vesicle stimulates association of v-SNARE with t-SNARE
- ) Membrane fusion is promoted by the interaction of v-SNARE with t-SNARE
- ) Binding of NSF and SNAPs promotes dissociation of the SNARE complex
(Vesicle Docking, Priming & Fusion)
Explained in 4 details:
1.) Tethering proteins help…
- ) The v-SNARE interacts with…
- ) The primed vesicle and membrane are thought to…
- ) In neurons, step 3 (fusion) is…
- ) hold the vesicles in position (docking)
- ) the t-SNAREs (syntaxin and SNAP25) bringing the vesicle membrane in close proximity to the presynaptic membrane (priming)
- ) possibly create an “unstable intermediate” or a “fusion stalk”
- ) the Ca2+-dependent step
(Vesicle Dynamics)
1.) The AP induces…
- ) The Ca2+ binds to…
- ) This triggers…
- ) The contents of the vesicle (i.e., neurotransmitter) is…
- ) an influx of Ca2+
- ) synaptotagmin
- ) the vesicle membrane to fuse with the cell membrane.
- ) released into the synaptic cleft.
Toxins that interfere with vesicle release: (3)
- ) Botulinum toxin (botox)
- ) Tetanus toxin
- ) Presynaptic blockers (inhibitors) of neurotransmission
(Botulinum toxin (botox))
1.) Causes…
- ) From…
- ) Botulinim toxins B,D,F and G will…
- ) Botulinum toxins A & E will…
- ) Botulinum toxin C1 will…
- ) Results in…
- ) botulism poisoning
- ) the bacterium Clostridium botulinum
- ) cleave synaptobrevin (VAMP, the v-SNARE)
- ) cleave SNAP-25 (t-SNARE)
- ) cleave Syntaxin (t-SNARE)
- ) paralysis
(Tetanus toxin)
1.) From the…
- ) Will…
- ) Results in…
- ) bacterium Clostridium tetani
- ) Cleave synaptobrevin (v-SNARE)
- ) rigid spasms due to effects in the CNS
After release, the neurotansmitters…
diffuse across the synaptic cleft and bind to receptors on the postsynaptic cell.
Neurotransmitter Receptor Classes: (2)
- ) Ionotropic: the receptor is a channel
- ) Metabotropic: the receptor communicates with a channel indirectly via some second messenger system (example G-protein)
Ionotropic Receptor Examples: (2)
- ) Nicotinic acetylcholine receptor (nAchR)
2. ) GABAa receptor
(Ionotropic Receptor Example/Nicotinic acetylcholine receptor (nAchR)
1.) Is a large…
- ) Normal ligand =
- ) Can also be…
- ) Will…
- ) Found at…
- ) Can be bound and inhibited by: (3)
- ) ligand-gated Na+ channel
- ) = acetylcholine (neurotransmitter)
- ) activated by nicotine (agonist)
- ) Induce depolarization of postsynaptic cell (EPSP), (see ENa+)
- ) the NMJ
- ) - a-bungarotoxin
- Cobratoxin
- Postsynaptic blockers or inhibitors (antagonists) of neurotransmission
(Ionotropic Receptor Example/GABAa receptor)
1.) Is a…
- ) Normal ligand =
- ) Opening of…
- ) Result in…
- ) Found in…
- ) Valium (Diazopam) enhances…
- Resulting in…
- ) Ligand-gated Cl- channel
- ) = GABA (neurotransmitter)
- ) the Cl- channel leads to hyperpolarization (see ECl-)
- ) an IPSP (decreasing the chance that the postsynaptic cell will fire and AP)
- ) the brain
- ) the effect of GABA by binding to the GABAA receptor (allosteric interaction)
- CNS depression
Metabotropic Receptor Example:
GABAb receptor (GABA is neurotransmitter)
(Metabotropic Receptor Example/GABAb receptor)
1.) Is a…
- ) Indirectly leads to…
- ) Results in…
- ) Found in…
- ) Activation results in…
- ) G-protein coupled receptor
- ) opening of a K+ channel results in hyperpolarization (see EK+)
- ) an IPSP (decreasing the chance that the postsynaptic cell will fire and AP)
- ) the brain
- ) CNS depression
(Postsynaptic Potentials)
1.) The electrical potentials induced by…
- ) Always…
- ) Occur usually at…
- ) May be…
- ) Or may be…
6.) They are additive in…
(+ 2 examples)
- ) neurotransmitters binding to specific neurotransmitter receptors.
- ) graded potentials (i.e., not APs)
- ) Dendrites or Soma.
- ) excitatory (depolarizing towards threshold) – Excitatory Postsynaptic Potentials (EPSPs).
- ) inhibitory (hyperpolarizing away from threshold) – Inhibitory Postsynaptic Potentials (IPSPs)
- ) time and space (temporal spatial summation)
- Spatial Summation
- Temporal Summation
The activation state of the postsynaptic cell is determined by
the net influence of all of the excitatory and inhibitory influences that are active.
Each IPSP and EPSP is a
graded potential that summate with all other inputs in the temporal spatial manner.
- Incoming electrical signals at the dendrites and the soma are…
- Not…
- May be…
- They spread to…
- They decay with…
- However, they are…
- If a sufficient level of depolarization occurs in the soma and dendrites such that the axon hillock depolarizes to the threshold value, then…
- graded potentials (IPSP and EPSP)
- APs
- fairly large
- adjoining regions passively
- time and distance
(Length constant, lambda/Time constant, t) - additive summation
- an AP will be generated there and then propagated along the axon
Why can’t the dendrites or soma fire APs?
????
Therefore, the AP is generally initiated at the Axon Hillock???
Review Neuron Regions (Functional Perspective) chart
screenshottttt
Review Postsynaptic Potentials vs Action Potentials chart
screenshottttt
- ) Neurotransmitters must be…
- ) In order to…
- ) Example:
- ) Located in…
- ) inactivated (or eliminated)
- ) prevent prolonged activation of the postsynaptic cell, neurotransmitters are degraded at the synapse
- ) Ex: acetylcholinesterase cleaves Ach into Acetate and choline
- ) the synaptic cleft or on the extracellular surface of the postsynaptic membrane
- GABA & Glutamate can be…
Take home message =
- transported into neurons and glia at synapses, eleminating them from the synaptic cleft.
= Neurotransmitters can be removed from the synapse by transport into cells (neurons and glia). Not all neurotransmitters are simply degraded like Ach.
