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BIOB50H3 (47)
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Chapter 4

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Biological Sciences
Ted Petit

Chapter 4: Neuron Structure and Function Continuation Signals Across the Synapse:  Once action potential reaches the axon terminal, the neuron transmits the signal across the synapse to target cell  The cell that transmits the signal is called presynaptic cell  The cell that receives the signal is called postsynaptic cell  The space between the presynaptic and postsynaptic cell is called synaptic cleft (three components make up the synapse)  The synapse between a motor neuron and a skeletal muscle cell is called neuromuscular junction Intracellular Calcium regulates neurotransmitter release:  When an action potential reaches the membrane of the presynaptic axon terminal of the neuromuscular junction, the depolarization causes the opening of voltage gated calcium channels  The concentration of calcium inside the neuron is lower compared to outside o This favours the calcium to go inside the cell  The increased calcium concentration inside the axon terminal creates a signal to the neurotransmitter- containing synaptic vesicles o These vesicles are grouped into two groups: a readily releasable pool and a storage pool o The releasable pool: is located at active zone and bound to the docking proteins, ready to release their content by exocytosis o The storage pool consists of vesicles bonded to the cytoskeleton  The calcium signal causes the vesicles from the readily releasable pool to fuse to the plasma membrane and release their contents  The calcium signals also causes the vesicles from the storage pool to move to the active zone of the plasma membrane and bind to the docking proteins in anticipation for the release  The vesicles contain neurotransmitter  As the action potential frequency increases, more vesicles move towards to the membrane and release content by exocytosis  The amount of neurotransmitter released from a neuron increases with each step corresponding to the content of a vesicle rather than increasing in a graded fashion (one molecule at a time) o This is called quantal release of neurotransmitters Action potential frequency increases neurotransmitter release  The amount of neurotransmitter released at synapse is correlated with the frequency of the action potential o weak signals due to low frequency action potential, thus fewer synaptic vesicles release the content  How is action potential and neurotransmitter released correlated? o Once the action potential arrives at the axon terminal, the calcium enters through the voltage gated channel o This calcium quickly binds to the intracellular buffer or is removed from the cytoplasm. This keeps the concentration of calcium low and limits the release of the neurotransmitter o When action potential arrives at the axon terminal, the calcium concentration increases inside because there is more influx than the removal o The increase calcium proves a stronger signal to exocytosis Acetylcholine is the primary neurotransmitter at the vertebrate neuromuscular junction:  Vertebrate motor neurons release the neurotransmitter acetylcholine into the synapse  Ach is a biogenic amine that is synthesized from amino acid and choline  ACh synthesis occur in the axon terminal by the enzyme choline acetyl transferase  Acetyl CoA from mitochondria combines with the amino acid choline to form ACh and coenzyme A  ACh is packaged into synaptic vesicles and stored until there is an action potential, which then diffuses into the synapse and binds to the receptor on the postsynaptic cell membrane Signaling is terminated by acetylcholinesterase  The signaling between a ligand such as a neurotransmitter and its receptor must be terminated to be effective  The enzyme in the synapse called acetylcholinesterase; removes the ACh from the receptor and breaks down ACh into choline and acetate  Choline is taken up by the presynaptic neuron and reused to create ACh and the acetate diffuses out of the synaptic cleft  Acetylcholinesterase plays an important role in regulating the strength of the signal to the postsynaptic cell by regulating the concentration of the neurotransmitter Postsynaptic cells express specific receptors:  Postsynaptic cells detect the neurotransmitter using specific cell-surface receptor  When a neurotransmitter binds to the receptor, the receptor changes shape  The change in shape of the receptor acts a signal to the target cell  The skeletal muscles called nicotinic ACh receptors, have the ability to bind to the drug nicotine o Nicotinic ACh receptors are ligand-gated ion channels o ACh binds to the receptor, receptor changes shape and allows ion to go across the membrane o The Nicotinic ACh receptors contain o Nicotinic ACh receptors have a channel that is permeable to potassium and sodium; the graded potentials in the postsynaptic cell is caused by high driving force of sodium influx  ACh build up in the nicotinic receptors on the skeletal muscles causes a rapid excitatory postsynaptic potential because of the influx of sodium depolarizes the postsynaptic muscle cell Neurotransmitter amount and receptor activity influence signal strength  Small amount of neurotransmitter provide small responses in the postsynaptic cell  As the neurotransmitter concentration increases, the response of the postsynaptic cell increases until the receptors are saturated  The concentration of neurotransmitter in the synapse is due to the balance between the rate of neurotransmitter from the presynaptic cell and the rate of removal of the neurotransmitter after the synapse  The removal of the neurotransmitter from the synapse depends on: 1. Neurotransmitter can diffuse passively out of the synapse 2. Surrounding cells, including presynaptic neurons, can also take up neurotransmitter-these cells act as regulators for neurotransmitters 3. Enzyme present in the synapse can degrade neurotransmitters  The response of the postsynaptic cell also depends on the number of receptors on the target cell o if there is a low number of receptors the neurotransmitter will cause a weak response o The density of the receptors on the postsynaptic cell can be regulated by genetic variation, metabolic state etc.  Myasthenia gravis is a disease caused by the alteration in receptor number on muscle cell o These people are very tired because antibodies from a person’s immune system destroy ACh receptors at the neuromuscular junction o The decrease amount of receptors, reduces the signal in the postsynaptic muscle cell  The symptoms of myasthenia gravis can be treated with acetylcholinesterase inhibitors o By inhibiting acetylcholestrase, these drugs reduce the rate of removal of ACh from the receptors and increase the concentration of ACh in synapse o These chemicals work by inhibiting the degradation of Ach by acetylcholinesterase o At high dosage you will be increase the concentration of ACh in the synapse causing over excitation in the muscle and producing twitching etc. Diversity of Neural Signaling:  Neurons perform 3 functions: they receive and integrate incoming signals, they conduct these signals through the cell and they transmit these signals to other cells  Some neurons are specialized to detec
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