3 3 Chemical Synapses When ligand and mechanically gated channels in the dendrite and soma membrane are activated they open and close ion channels changing the permeability of the membrane to ions These changes in ion currents result in graded passive potentials that can sum up at the axon hillock and potentially initiate an action potential sending a signal of activation shooting down the axon to whatever the neuron is targeting By now this should be a familiar story But where do those chemical and mechanical stimuli come from What happens when the action potential arrives at the axon terminal In many cases the answer is the same a chemical signal is released from the axon terminal of one neuron to the dendrite or soma of the next For now we will focus on chemical stimuli and ligand gated channels Where one neuron contacts another is a synapse There are electrical synapses and chemical synapses where either electrical or chemical signals flow from one neuron to the next We will focus on chemical synapses for now Between the axon terminal of the pre synaptic neuron and the membrane of the post synaptic neuron there is a very small space called the synaptic cleft When an action potential arrives at the axon terminal of the pre synaptic neuron chemical signals called neurotransmitters are released from the axon terminal which diffuse across the synaptic cleft and bind receptors in the membrane of the post synaptic cell initiating a graded potential In this way signals are transduced from electrical to chemical to electrical as they go from neuron to neuron Recall that the action potential in the pre synaptic neuron will be all or none however neurons are able to send information about intensity Instead of varying the magnitude of their action potentials they vary the frequency When a neuron fires several action potentials close together this will result in a greater amount of neurotransmitter being released into the synapse Although it is prevented from firing during its absolute refractory period if it receives sufficient stimulation it can fire during the relative refractory period before it is completely repolarized How do action potentials result in neurotransmitter release and why does increasing the frequency of one increase amount of the other In the membrane of the axon terminal there is another type of voltage gated channel a voltage gated Ca2 channel When the action potential arrives at the axon terminal this will open voltage gated Ca2 channels Because Ca2 is much more concentrated outside the cell than inside such that the Keq 130 mV it will diffuse in Also inside the axon terminal are membrane bound packages of neurotransmitter that have been synthesized by the cell Some of these packages or vesicles are docked at the inside of the membrane by Ca2 sensitive proteins When Ca2 comes into the cell it will interact with these docking proteins causing the vesicle to fuse with the membrane and exocytose the neurotransmitter into the synaptic cleft Ca2 is then pumped out of the cell against its concentration gradient by Ca2 ATPases not shown in the figure below We know that each vesicle contains about the same amount of neurotransmitter and each of these packages corresponds to about the same amount of change in the post synaptic potential Without Ca2 a pre synaptic cell will randomly release a vesicle or two and we can measure the small changes in post synaptic potential that these events cause We see discrete units of change that correspond to the number of vesicles that emptied their contents into the synapse as shown in 2 the graph below The role of Ca2 is to coordinate many of these vesicles to fuse at once causing a graded post synaptic potential that is many units large When multiple action potentials are fired in a short time the neuron does not have enough time to return the intracellular Ca2 to normal Thus as the membrane at the axon terminal continues to depolarize Ca2 accumulates inside causing more vesicles to fuse with the membrane and more packages of neurotransmitter will be released There are many different chemicals that qualify as neurotransmitters In general a neurotransmitter is something that 1 Is synthesized inside the pre synaptic neuron 2 Is released by the pre synaptic neuron into the synaptic cleft 3 Elicits a post synaptic response that can be mimicked by artificially applying the chemical to the synapse 4 Has a mechanism for being removed from the synaptic cleft Many neurotransmitters are synthesized by the cell from scratch using building blocks that the cell absorbs from its environment or are products of metabolism This includes most small neurotransmitters such as biogenic amines derived from amino acids Small neurotransmitters are often synthesized right in the axon terminal then packaged into vesicles Neuropeptides on the other hand are large protein neurotransmitters that are products of translation For each neuropeptide there is a gene that encodes for an mRNA that is translated and processed to make the mature neurotransmitter Thus at least part of their biosynthesis must occur in the nucleus Translation can then occur wherever ribosomes are Some neuropeptides have mRNA transcripts that are transported by the cytoskeleton all the way from the nucleus in the soma down the axon to the axon terminal where they are translated locally The original sequence of amino acids is actually chopped up twice by enzymes before the mature neuropeptide is made The initial translation product is the prepropeptide which is processed enzymatically to make the propeptide which is processed to make the mature peptide Many neurons synthesize only one type of neurotransmitter Thus you will often hear neurons described by the neurotransmitter they make and release e g dopamine neurons or serotonin neurons However we are discovering that some neurons synthesize more than one neurotransmitter often one small and one large The neuron knows which one to release by the frequency with which it is being stimulated If it is being stimulated at a low frequency it will release its smaller neurotransmitter At a high frequency of stimulation the large neurotransmitter will be released There are many details of this process that we still do not know When a NT is released by the pre synaptic cell it must have a corresponding receptor in the membrane of the post synaptic cell Once it binds its receptor the neuron transduces this chemical signal into an electrical signal by
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