Synaptic Transmission Flashcards
What is the nernst equation?
This relates the numerical values of the concentration gradient in a half cell to the electrical gradient that balances it.
What is electrical synaptic transmission?
This is basically a mechanism for coupling/synchronizing cells to fire together. This is permitted through the flow of ions through gap junctions.
what is a limitation of electrical synaptic transmission, as opposed to chemical transmission.
1) Can’t be amplified. 2) always excitatory so you can’t get complex integration of excitatory and inhibitory synaptic inputs 3) can’t really modulate the signal (no learning and memory at electrical synapses)
Why is electrical synaptic transmission ineffective at the neuromuscular junction?
because the nerve terminal is so much smaller than the muscle fiber it innervates, it can’t provide enough current to depolarize the muscle.
Is electrical synaptic transmission impt in the mammalian CNS?
not really, pretty rare.
Name examples of electrical synaptic transmission.
escape reflexes, heart and smooth muscle, development of retina, inner ear, CNS: fear learning, emotional memory in hippocampus, contribution to the establishment of (alert) theta rhythms
Name the presynaptic events involved in transmitter release, from the time of the arrival of an action potential to exocytosis.
action potential arrives in the presynaptic terminal –> depolarization causes voltage gated calcium channels to open, calcium ions flow down their electrochemical gradient int o the cell –> binding of calcium ions to protein syanaptotagmin triggers fusion of the lipids of the vesicle and surface membranes –> opening a fusion pore through which the neurotransmitter diffuses out of the vesicle
Describe presynaptic events involved in cleanup operations, both outside the cell and inside the cell. Eg, for calcium.
Calcium –> pumped out of cell by 2 types of pump, one is driven by ATP (primary active transport), another is a sodium-calcium exchanger (antiporter; secondary active transport).. Finally, sodium-potassium pumps and calcium pumps in muscle surface membrane extrude sodium and calcium and reabsorb potassium.
how does tetanus toxin work?
selectively blocks inhibitory synaptic transmission produce powerful persistent, involuntary skeletal muscle contractions. Does this by selective cleavage of a protein component of synaptic vesicles called synaptobrevin II, and this prevents the release of neuro transmitters by the cells. Thus, it clips SNARES, and in so doing interferes with exocytosis.
how does botulinum toxin work?
blocks vesicular fusion in presynaptic cholinergic neurons, thereby preventing the release of ACh into the synaptic cleft. It does this by CLIPPING SNARE PROTEINS (synaptobrevin, syntaxin, SNAP-25, depends on the strain) and thus interfering with exocytosis
Name the postsynaptic events involved in synaptic transmission
liberated molecules of neurotransmitter bump into the postsynaptic membrane –> bind to receptors in postsynaptic membrane –> initiates postsynaptic response. Meanwhile, membrane is reinternalized (endocytosed) and refilled with neurotransmitter.
What is the ‘job description’ for a motor nerve terminal?
Every time an action potential arrives from the CNS, the nerve must secrete enough ACh to depolarize the muscle by about 30 mV. Too little and it won’t stimulate the muscle to contract, too much and the muscle fiber will only contract once.
Describe how the neuromuscular synapse amplifies the incoming signal in order to depolarize the muscle fiber to threshold for an action potential.
1) each synaptic vesicles contains several thousand ACh molecules. Each receptor that is activated, permits the flow of about 1000 positive charges into the muscle fiber. 2) synaptic terminal is bulked up – a) length of contact with muscle is extended b) has a few hundred active zones c) has tens of thousands of synaptic vesicles
What is the safety factor at the NM junction? Do CNS synapses have safety factors as well? Why/why not?
motor nerve terminal secretes the contents of a few times more than the minimum number of synaptic vesicles needed.
Define facilitation and synaptic depression of transmitter release. Name the underlying mechanism of each.
Facilitation –> during repetitive simulation, calcium ion concentration in the presynaptic terminal builds up because it can’t be cleaned up as fast, this results in increased exocytosis. So residual calcium (calcium that hasn’t been pumped out from previous action potentials) increases number of quanta secreted. Synaptic depression –> nerve terminal runs out of releasable vesicles, so number of quanta secreted decreases.
Describe the basic mechanism that determines whether a synapse is direct (fast) or indirect (slow). Name a typical physiological response mediated by each.
fast (direct) –> neurotransmitter directly gates an ion channel, which instantly changes membrane permeability. slow (indirect) –> neurotransmitter receptor protein is not an ion channel but rather a protein channel that undergoes a structural rearrangement, then G protein senses the conformational change and initiates a series of events that ultimately leads to a change in ion channel behavior. NMJ = Fast, CNS= fast or slow.
Describe the conductance (permeability) characteristics of the channel opened in fast excitation.
ACh receptor channels at the NMJ are permeable to all CATIONS. It is thus called a Non-Selective Cation channel.
Define the electrical “driving force.”
This is voltage, which is the difference in electrical potential across the cell.
Define the reversal potential for direct excitation.
Since NSC channels are nonselective to all cations, opening an infinite number of these channels would drive the muscle fiber membrane potential to a value between Ena and Ek. This is defined as the reversal potential.
Describe the kind of channel that is opened during fast inhibition in the CNS.
ionotropic, NSC channel.
Why is inhibition often more powerful than one might predict from the size of an individual inhibitory post-synaptic potential (IPSP)?
This is because he effect of an IPSP depends on the relative permeabilities of each participating ion. It depends on the ion’s equilibrium potential in relation to the resting potential. Eg. chloride.
Define temporal and spatial summation of postsynaptic potentials.
spatial summation - 2 or more different inputs (excitatory synaptic inputs) summate to drive a motor neuron to fire an action potential simultaneoulsy. temporal summation - same input is stimulated in succession.
Describe the 3 mechanisms for removing transmitters from synaptic clefts.
1) diffusion out of the cleft and into surrounding ECF 2) recyling – molecules are pumped back into the presynaptic terminal by specialized sodium-coupled cotransporters 3) destroyed (eg ACh). acetylcholine esterase cleaves ACh, producing acetate and choline.
What is a coincidence detector? How does the NMDA receptor work as a coincidence detector?
Type of receptor that require not only glutamate (to open the glumate activated gate) but also a postsynaptic action potential (to remove the mg ion). NMDA receptors also have a high permeability to calcium ions.
How can activation of NMDA receptors lead to synaptic strengthening?
Through a couple different mechanisms – 1) activation of NMDA receptors causes Ca++ influx, which triggers exocytosis of vesicles that insert additional AMPA receptors into the postsynaptic membrane. 2) can also occur presynaptically through retrograde signal from the postsynaptic cell to the presynaptic terminal. entry of calcium ions through NMDA receptor channels into the postsynaptic dendrite promotes synthesis of NO, which diffuses back across the synapse and potentiates transmitter release.
How might such a mechanism (synaptic strengthening as a consequence of NMDA activation) lead to behavioral associative conditioning?
conditioned stimulus is paired with unconditioned stimulus. Strong input from UCS rmakes in AP in the output cell that pops open the Mg++ ion out of the NMDA channel pore, but only at selective CS synapse, which can then activate the output cell.
What is LTP, what is LTD? How are they involved in learning and memory?
LTD – with low frequency stimulation, synaptic responses become smaller and stay smaller. (mechanism probably involves retrieval of AMPA receptors from the postsynaptic membrane, which then become less sensitive to glumate secreted by the presynaptic terminal. LPD – instead of the postsynaptic vesicle secreting transmitter, it inserts additional AMPA receptors into the postsynaptic membrane, which increases the size of glutamate-induced synaptic potentials.
major excitatory transmitter in the CNS
glutamate
major inhibitory transmitter in the CNS
GABA, which acts by increasing chloride permeability in the postsynaptic membrane.
nicotinic receptors
ACh receptors (also activated by nicotine) that is a NSC and produces fast synaptic potentials.
muscarinic receptors
ACh receptor coupled to a G protein that is indirect/slow
synaptic integration
summation of excitatory and inhibitory potentials in neurons
trigger zone
junction between cell body and the axon where action potentials always arise. also called axon hillock/initial segment
how does presynaptic inhibition of transmitter release work?
This occurs with inhibitory nerve terminals that synapse on other excitatory presynaptic terminals (creating a sandwich). Action potential in inhibitory terminal (#1) releases GABA, which opens chloride channels in the target presynaptic terminal. Open chloride channels reduce the number of voltage-gated Ca channels that open in response to the action potential. Net effect is to reduce neurotransmitter release. This provides a mechanism to selectively shut off certain inputs to a cell without affecting its resting membrane potential.
examples of deficiencys in electrical synapse transmission
charcot-marie-tooth neuropathy
