NRS 250 Final - The Chemical Synapse

Steps in Chemical Signaling 

• Step 1: Action potential reaches the axon terminal, depolarizing the membrane. 

• Step 2: Voltage-gated calcium channels open; Ca²⁺ floods into the terminal. 

• Step 3: Synaptic vesicles dock at the membrane via SNARE proteins. 

• Step 4: Vesicles fuse and release neurotransmitter into the synaptic cleft (exocytosis). 

• Step 5: Neurotransmitter binds to receptors on the postsynaptic membrane. 

• Step 6: Postsynaptic potentials are generated (EPSPs or IPSPs). 

• Step 7: Neurotransmitter is inactivated via enzymatic degradation, reuptake, or diffusion. 

Presynaptic: What is quantized neurotransmitter release? 

• Quantized release means neurotransmitters are released in discrete packets called quanta. 

• Each quantum corresponds to the contents of one synaptic vesicle. 

• Miniature end plate potentials (mEPPs) reflect spontaneous single-vesicle release. 

• The number of vesicles released during evoked activity varies randomly (follows a binomial distribution). 

• Calcium influx increases the probability of vesicle fusion, but does not guarantee it. 

Postsynaptic: What causes PSPs? How are EPSPs and IPSPs different? 

• PSPs result from neurotransmitter binding to receptors, causing ion channels to open. 

• EPSPs (excitatory): Cause depolarization (cell becomes more positive, more likely to fire). 

• IPSPs (inhibitory): Cause hyperpolarization (cell becomes more negative, less likely to fire). 

• Ions involved include Na⁺ (inward, depolarizing) and Cl⁻ or K⁺ (outward or inward, hyperpolarizing). 

• PSPs occur primarily on dendrites and summate at the axon hillock. 

What is summation? 

• Summation is the process where multiple PSPs combine to influence whether a neuron fires. 

• Temporal summation: Rapid, repeated signals from one synapse add together. 

• Spatial summation: Simultaneous input from multiple synapses adds together. 

• If combined input reaches threshold, it triggers an action potential. 

Ionotropic vs. Metabotropic Receptors 

• Ionotropic receptors: Ligand-gated ion channels; open directly when neurotransmitter binds. 

• Fast and short-acting (milliseconds). 

• Example: Glutamate or GABA receptors. 

• Metabotropic receptors (GPCRs): Do not form channels; activate G-proteins which trigger signaling cascades. 

• Slower onset, longer-lasting effects. 

• Can cause widespread metabolic changes in the neuron. 

What are G-proteins and the G-protein cycle? 

• G-proteins are made of α, β, and γ subunits. 

• Inactive state: Bound to GDP. 

• When activated by a receptor, GDP is replaced by GTP → G-protein becomes active. 

• The α-subunit and βγ-complex then activate downstream effectors (e.g., enzymes or ion channels). 

• The GTP is hydrolyzed back to GDP to inactivate the G-protein. 

Describe the Phospholipase C, IP3, DAG, Protein Kinase C cascade 

• Gαq activates Phospholipase C (PLC). 

• PLC splits PIP₂ into IP₃ and DAG. 

• IP₃ causes release of Ca²⁺ from intracellular stores (ER). 

• DAG stays in the membrane and activates Protein Kinase C (PKC). 

• PKC phosphorylates target proteins, altering neuronal activity and function.