2.2.4. Muscular Junctions Flashcards
Types of Physiological Depolarization
- Synaptic transmission
- Spontaneous (i.e., pacemaker cells)
- Another action potential
- Peripheral receptors
What parts of the neuron have elevated thresholds?
The cell bodies and dendrites (compared to the axon hillock aka “trigger zone”)
Where are acton potentials usually generated?
The axon hillock?
Resting potential of the CNS
-65 mV
Initial Segment Threshold
AKA axon hillock trigger zone
-45 mV
Soma-Dendrite Threshold
-30 mV
Role of the axon hillock
Sums the synaptic activity in the cell (if the result is depolarization to threshold, the cell fires)
Does the distance of the synapse from the axon hillock influence depolarization?
Yes, as does the cell membrane’s electrical properties
EPSPs
Excitatory Post Synaptic Potentials
Synaptic potentials that can depolarize the membrane above threshold and produce an action potential
IPSPs
Inhibitory Post Synaptic Potentials
Synaptic potentials that hyperpolarize the membrane OR stabilize the membrane hyperpolarized to threshold
What does hyperpolarized mean?
More negative
What does depolarized mean?
More positive
What are the Two Types of Synapses?
- Electrical
2. Chemical
Electrical Synapses
Direct spread of ionic current b/w the axoplasm of the pre and postsynaptic cleft. Physical continuity b/w cells
Chemical Synapses
Chemical transmitter is released and diffuses across the space b/w the pre and postsynaptic cell. No physical continuity b/w cells
Where are electrical synapses most commonly found?
Cardiac Muscle, Smooth Muscle, and the Gut
Used in places that do not usually require fast modification (stereotyped)
Gap Junctions
Form bridges b/w the axoplasm of the pre and postsynaptic cells. At the electrical synaptic junction, the cell membranes are closer together than normal cell separation
What are Gap Junctions in the Heart called
Intercalated Discs
Connexons
Allow ion and small molecules to pass b/w pre and postsynaptic cells (one connexon is contributed by each cell)
Properties of an Electrical Synapse
- Reduced extracellular space
- Cytoplasmic continuity
- Ionic current
- Bidirectional
- Stereotyped
Where is Chemical Synaptic Transmission commonly found?
CNS (used where behavior must be flexible)
What unique feature distinguished Chemical Synapses from Electrical ones?
Their capacity to amplify signal. Axons branch and form many synapses (one axon may produce APs in hundreds of postsynaptic cells)
Channel associated with the presynaptic cell
Voltage-Gated Ca channel
Channels associated with the postsynaptic cell
- Voltage-Gated Action Potential K channel
- Voltage-Gated Action Potential Na channel
- Postsynaptic Receptor Channels
What does action potential depolarization cause?
Calcium influx (down its electrochemical gradient into the presynaptic cell)
Calcium interaction with vesicles
Causes vesicles to migrate to the presynaptic membrane and fuse, leading to transmitter release into the synaptic cleft
Presynaptic Calcium Characteristics
- Big, inward concentration gradient (exception is SR)
- Opening of channels are much slower than Na channels
- Calcium acts more as a messenger than a real ion (except in Cardiac Muscle)
- The amount of calcium entering the cell controls the amount of transmitter released
Two types of transmitter/postsynaptic receptor interaction
- Ionotropic
2. Metabotropic
Ionotropic
Directly opens or closes a channel in the postsynaptic membrane
Metabotropic
Releases a messenger (usually a G-protein) and most commonly activates secondary channels in the membrane
What determines ionic flow through open channels in ionotropic interaction?
- Channel selectivity
2. Electrochemical gradients
The Neuromuscular Junction
Interaction of ACh with the postsynaptic receptor produces an End Plate Potential (EPP)
Each muscle fiber is innervated by only one motor neuron. Healthy muscle has receptors only at the end plate.
EPP
End Plate Potential
Basically and EPSP at the neuromuscular junction. Interaction of ACh with the receptor opens a channel that becomes equally permeable to both Na and K (specificity is low so most positively charged ions can pass through)
Negatively charged excluded
What direction do Na and K flow?
Into the cell and out of the cell, respectively (down their electrochemical gradients)
Conductance of Na and K during an EPP
They are equal
Between Na and K, which ion has the larger driving force?
Na (this is why more sodium enters the cell than potassium leaves, leading to depolarization)
Physiological ways to inhibit the EPP
NONE. It is always excitatory
What is the muscle fiber threshold?
Around -60 mV
The amplitude of the EPP is ALWAYS large enough to depolarize the muscle fiber super-threshold. If EPP doesn’t produce a muscle action potential, you’re sick.
How many channels open during an EPP?
~2x10E5, resulting in 60 mV EPP
Opening of 1 channel would produce a potential of only ~0.3 microVolts
Differences b/w the EPP and EPSP
The PSP in the CNS is rarely larger than 1 mV in amplitude (need many EPSPs to bring a CNS cell to threshold)
PSP can be excitatory or inhibitory (IPSP)
How is ACh regulated?
Acetylcholinesterase (AChE), which is present at the synaptic cleft
It splits ACh into Acetate and Choline
How does the postsynaptic potential decay?
Via the non-gated leakage channels in the postsynaptic membrane
What are the fates of Acetate and Choline
Acetate diffuses out of the synaptic cleft and into extracellular fluid
Choline is recaptured by the presynaptic terminal via secondary, active co-transport using energy stored in the sodium gradient
Membrane Recovery
Newly formed vesicles are able to migrate back into the presynaptic terminal to be refilled with transmitter
EPP and PSP Electrical Properties
EPSPs, IPSPs, and EPPs spread electronically
- They DO NOT propagate (currents and voltages decay from its point of origin both in time and distance)
- They have no regeneration properties
Action Potential vs. PSP % EPP
Action Potential: activated by voltage, propagates, channels are separate for Na and K, regenerative, no summation
EPSP/IPSP/EPP: activated by transmitter, no propagation, same channels for Na and K, not regenerative, can sum
MEPP (transmitter release at the End Plate)
Miniature End Plate Potential
The result of the contents from 1 synaptic vesicle being released. Has an amplitude of ~0.5 mV (a full blown EPP has an amplitude of 60 mV or ~150 vesicles)
A CNS postsynaptic potential can be produced by?
- Opening a normally closed channel in the membrane (EPSP)
2. Closing a normally open channel in the membrane (IPSP)
Ionotropic EPSP (CNS)
Behavior is exactly like the neuromuscular junction except for the amplitude of the EPSP (which is only 1-2 mV). Increased permeability to both Na and K
Ionotropic IPSP (CNS)
Increased permeability for Cl or K (increasing the permeability for an ion moves the membrane potential toward the equilibrium potential for that ion).
In many cases, inhibition is achieved by hyperpolarizing the cell
Metabotropic EPSP (CNS) via channel closure
Example: closing a normally open K channel
The resting potential is normally maintained almost exclusively by non-gated, K leakage channels. In some neurons there are additional, transmitter-gated K channel complexes (closing these channels brings the membrane closer to threshold producing an EPSP)
Where are most of the action potential synapses located in the CNS?
On the dendritic tree; however, some are located on the cell body
The axon proper is usually devoid of synapses
What are the two types of summation in the CNS?
- Temporal
2. Spatial
Temporal Summation
Rapid firing of a single synapse to bring the cell to threshold
Spatial Summation
Simultaneous firing of many synapses to bring the cell to threshold
EPSP-IPSP Summation
The hyperpolarizing current from one synapse cancels some of the depolarizing current from another synapse and the membrane doesn’t reach threshold
No Action Potential
Drugs that stimulate the muscle fiber by ACh-like action
Methacholine, Carbachol, and Nicotine
Not degraded by AChE; action often persists for hours (constant stay of muscle spasms)
Drugs that stimulate the muscle fiber by AChE inactivation
Neostigmine, Physostigmine, and Diisopropyl fluorophosphate (DFP)
Prevent ACh-ase from hydrolyzing ACh (muscle spasm/over-activation)
Drugs that block transmission at the neuromuscular junction
Group of drugs called “curariform drugs” can prevent signal propagation from the nerve ending onto the muscle
Myasthenia Gravis
Autoantibodies against the ACh receptor on the postsynaptic membrane. Muscle weakness that worsens with use and improves with rest.
Associated with thymic hyperplasia or thymoma (thymectomy improves symptoms)
What are the classic symptoms of Myasthenia Gravis?
Ptosis (droopy eyelids) and Diplopia (double vision)
Improved with AChE agents
Lambert-Eaton syndrome
Antibodies against the presynaptic calcium channels. Leads to impaired ACh release (vesicle fusion with the membrane does not occur)
What does Lambert-Eaton syndrome typically arise from?
As a paraneoplastic syndrome, most commonly due to small cell carcinoma of the lung
Clinical features of Lambert-Eaton syndrome
Muscle weakness that improves with use (eyes usually spared). AChE agents DO NOT improve the symptoms.
Resolves with resection of the cancer.
