Helena Parkington; Week 9 MED1011; Physiology
At synapses there are terminal boutons where transmitter release occurs. Boutons contain vesicles which are released into the synaptic cleft to reach the post-synaptic neuron. Vesicles are anchored to filaments in bouton, some vesicles are positioned in docking sites. Synapse is about 20nm wide, transmitter removal occurs here. Vesicles dock on docking proteins for release beside calcium channels. On Ca influx, neurotransmitter is released. Synaptic receptors have 5 subunits, each with 4 membrane spanning regions which are in high concentrations on post-synaptic membrane. Used by excitatory transmitters (ACh, glutamate) and inhibitory (GABA, glycine) transmitters. TM (transmembrane) 2 segments lie close together at rest, form a pore, move apart to form a hole when transmitter binds. Allows ions to pass through when opened (ionotropic). Come together again to close the ion channel. There is a large extracellular domain to which neurotransmitter binds, concentrated in synaptic region, called ionotropic receptors.
Activation of receptor turns it into a channel, Na enters and K leaves 4:1 at -60mV leading to a net positive ion influx. Cell membrane is depolarised, excitatory post-synaptic potential is the response. It is a graded response, the greater the number of channels opened the larger the EPSP. Vesicles contain approximately the same amount of neurotransmitter per vesicle, results in EPSPs of approximately equal amplitude. An EPSP on a dendrite is very fast, has a change of chaperone, decays. Length constant of an axon is the distance at which voltage declines to about 37% of its original value. EPSP that is sufficiently large reaches threshold and increases the probability of opening voltage activated Na channels.
NMDA is a glutamate receptor that acts post synaptically, has ion channel blocked with Mg ions if voltage is insufficient. AMPA is another, different, glutamate receptor. Inhibitory ionotropic receptors release Cl, often in response to glycine. This causes hyperpolarisation when the voltage is less than -74mV (no change when more negative but will cancel out incoming positive). Increase in K conductance also causes hyperpolarisation, down to -94mV.
Temporal summation is two impulses at same area one after the other adding up to threshold. Spatial summation is two impulses at different places adding up to one. Spatial summation can also occur temporally if one is at cell body and one is at dendrite. Simple inhibition is two temporal neurons with opposite effects. Presynaptic inhibition can be one synapse acting on another to inhibit it from conducting. Facilitation is where the second EPSP is larger than the first and is generally caused by residual calcium in the bouton causing accumulation.
Chance of a docked vesicle fusing with the plasma membrane and releasing transmitter when the action potential invades is between 1 and 0 (never releases), can be influenced by use of the synapse. Use increases probability of release, increases the size of synapse (presynaptic increased number of release sites; post synaptic density of receptors/channels). This forms the basis of long term potentiation.
Central neurotransmitters are glutamate (ionotropic NMDA, AMPA receptors, metabotropic receptors), ACh (excitatory ionotropic nicotinic receptors, muscarinic metabotropic receptors), catecholamines such as dopamine and NA act at metabotropic receptors, serotonin at metabotropic receptors. Presynaptic metabotropic receptors decrease probability of release, postsynaptic slow synaptic responses and there may be no change in receptor potential as a result. They are not usually located within the synapse, lower concentrations of transmitter used in activation, widely utilised by neurotransmitters. They have 7 membrane spanning regions with response transduced by G proteins. They have a slow response with change in membrane potential not necessary and small/slow response if present. This is in comparison to fast ionotropic receptors which always have a change in membrane potential.
Glutamate is excitatory ionotropic NMDA, AMPA and metabotropic receptors. ACh is excitatory ionotropic nicotinic receptors, muscarinic metabotropic. GABA is inhibitory ionotropic, as is glycine. ACh nicotinic receptor is associated with Alzheimers, myasthenia gravis and nocturnal epilepsy. Glycine is associated with absence epilepsy and startle disease. Glutamate NMDA is associated with stroke. Some diseases are associated with metabotropic such as Parkinson's at the dopamine receptor and serotonin in depression.
Synapses have memory, associated with long term potentiation and receptor increase/decrease.