Synapses and Synaptic Transmission Flashcards
Communication between cells occurs at specialized junctions called ______
synapses.
What are the main types of synapses?
- Electrical
- Chemical
What occurs at an electrical synapse?
At electrical synapses there is direct electrical continuity between the pre- and postsynaptic cell. A type of channel known as a gap junction forms a low resistance pore between the cells. Molecules known as connexins form a hemichannel in each cell, known as a connexon.
The connexons from the two cells join to form a gap junction. Electrical transmission is typically rapid (no delay), can be bidirectional, and requires matching between the size of pre- and postsynaptic cells)
What occurs at a chemical synapse?
An AP leads to release of a chemical transmitter which diffuses across a synaptic cleft to interact with ligand-gated channels in the postsynaptic membrane.
Thus an electrical signal is transduced into a chemical signal. Chemical transmission is unidirectional, there is a synaptic delay, and can change the sign of a signal or amplify a signal.
What are the main presynaptic steps of chemical transmission?
- Transmitter is synthesized and stored in vesicles in the synaptic terminal.
- An AP invades the terminal and depolarizes the terminal.
- The depolarization serves to open voltage gated calcium channels leading to influx of Ca2+
- Ca2+ causes fusion of synaptic vesicles with presynaptic membrane (via interaction with molecules known as SNARES). Release occurs in packets of a minimal size known as quanta. It is thought that the contents of 1 vesicle = 1 quanta.
- Transmitter is released into the synaptic cleft and diffuses across.
What are the main postsynaptic steps of chemical transmission?
- Transmitter binds to receptors (often ligand-gated channels).
- Opening or closing of ion channels occurs.
- Postsynaptic currents cause membrane potential change.
The neurotransmitter must then be either metabolized or taken up to end transmission.
Presynaptically, the vesicles are recycled and re-filled with transmitter.
At the neuromuscular junction (NMJ), chemical synaptic transmission is specialized for a high safety factor to ensure that every time a motoneuron releases transmitter, every muscle fiber it innervates has an AP and contracts.
To this end, there are many anatomical specializations (collectively called the end plate). There are many release sites for transmitter, high numbers of receptors, and high quantal content (basically the number of vesicles available for release) and high probability of release for each quanta, as well as high numbers of postsynaptic receptors.
At the NMJ, the neurotransmitter is acetylcholine (ACH) and the receptors are of the nicotinic type.
Most synapses in the CNS (right) are much simpler anatomically than the NMJ. How?
Quantal content is low and the safety factor is also low. The size of the post synaptic potentials (PSPs) are also typically small, thus requiring summation of many PSPs to reach threshold for an AP.
CNS synapses are also much more diverse than the NMJ – there are many different transmitters and responses can be either excitatory, inhibitory, or modulatory.
This slide illustrates some of the diversity of neurotransmitters found in the CNS. These molecules include peptides, amino acids, and biogenic amines.
Most fast transmission is mediated by amino acids
What CNS transmitters are inhibitory?
GABA, Glycine, Dopamine (D2)
Opiods, Metenkephalin
Serotonin can be both
All others are excitatory (e.g. ACh, Nor, Epi, Substance P, etc.)
What are the two types of chemical transmission?
- Fast transmission with Ligand-gated channels
- GCPR transmission
What mediates fast chemical transmission?
Fast transmission is mediated by ligands (transmitters in this case) binding to a ligand-gated channel.
Ligand-gated channels are an integrated receptor (where the binding site for transmitter is part of the same molecular complex as the channel). Binding of the ligand causes a conformational change in the channel, resulting in gating (activation). The key is that receptor and channels are part of the same molecular complex.
What are Neuromodulatory effects?
Effects that are not depolarization or hyperpolarization per se, but rather biochemical changes in the cell which alter function and/or excitability.
Neuromodulatory effects are mediated by what?
G-protein coupled receptors
Describe the srtucture of G-protein coupled receptors
These receptors have 7 transmembrane spanning regions and when they bind a ligand, a conformational change facilitates interaction with a G-protein. The activated G-protein the either interacts directly with an ion channel or indirectly via second messengers. Thus any effects of ligand binding on membrane potential are indirect via a signaling pathway. G-protein mediated effects can also be through effectors other than ion channels (e.g., enzyme).
As mentioned previously, when Ca2+ enters the synaptic terminal it interacts with proteins known as SNAREs (Soluble NSF Attachment Protein Receptor). What are some examples of SNAREs?
include Syntaxin, SNAP-25, and Synaptobrevin
What do SNAREs do?
These proteins facilitate docking of transmitter-filled vesicles at the membrane and prime the vesicles for release. They are located both on the synaptic vesicle (synaptobrevin) and the junction terminal (Syntaxin and SNAP 25)
What happens in Lambert Eaton Myasthenic Syndrome?
it is an autoimmune disorder where small cell carcinomas in the lung release antibodies against presynaptic calcium channels (L-type).
In a normal state, normal resting neurons use oxygen and glucose as basic substrates for glycolytic and mitochondrial production of ATP. In the resting state, how is glucose processed in neurons?
In the resting state, glucose enters brain cells and is metabolized through the glycolytic pathway to form pyruvate and lactate.
This particular synapse is a glutamatergic synapse but similar metabolic pathways occur at other neurotransmitter synapses, both excitatory and inhibitory. The release of glutamate by the presynaptic bouton on the left triggers postsynaptic membrane depolarization and ion shift in the postsynaptic cell. In addition, the glutamate released into the synaptic cleft must be taken back into cells and this occurs in an adjacent astrocyte. This reuptake of glutamate into astrocytes occurs via Na+ membrane transporters with a stoichiometry of 3 Na+ ions taken up for each glutamate molecule. This increase in intracellular Na+ activates the Na+ ,K ATPase pump to normalize intracellular Na+. The increased utilization of ATP, in turn, activates glycolysis, with the production of lactate. The substrate for glycolysis is glucose delivered to the astrocyte from the circulation. Lactate produced in the astrocyte can be transported to the pre and postsynaptic neurons for further metabolism back to pyruvate with additional generation of ATP.
- Lambert Eaton Syndrome
2.
2.
5.
Hyperkalemic periodic paralysis is a condition that causes episodes of extreme muscle weakness or paralysis, usually beginning in infancy or early childhood. Most often, these episodes involve a temporary inability to move muscles in the arms and legs. Episodes tend to increase in frequency until mid-adulthood, after which they occur less frequently. Factors that can trigger attacks include rest after exercise, potassium-rich foods such as bananas and potatoes, stress, fatigue, alcohol, pregnancy, exposure to cold temperatures, certain medications, and periods without food (fasting). Muscle strength usually returns to normal between attacks, although many affected people continue to experience mild stiffness (myotonia), particularly in muscles of the face and hands.
Most people with hyperkalemic periodic paralysis have increased levels of potassium in their blood (hyperkalemia) during attacks. Hyperkalemia results when the weak or paralyzed muscles release potassium ions into the bloodstream. In other cases, attacks are associated with normal blood potassium levels (normokalemia). Ingesting potassium can trigger attacks in affected individuals, even if blood potassium levels do not go up
- Either can occur
AR trait of gain of function mutation that prevents Na+ channels from inactivating
