Neurotransmitters and Action Potentials

Neurotransmitter Release and Action Potential Generation

  • Neurotransmitter Release

    • Neurotransmitters are released into the synaptic cleft and bind to receptor proteins on the postsynaptic plasma membrane.

    • If the neurotransmitter results in an excitatory postsynaptic potential (EPSP), it leads to an excitatory graded potential.

    • Graded Potentials:

    • Defined as depolarizations of variable strengths, i.e., they can vary in intensity.

    • Example ranges include:

      • Very weak: from -90 mV to -87 mV

      • Stronger: from -90 mV to -70 mV

    • Important to note that these potentials must sum collectively to reach a threshold level to trigger an action potential at the axonal hillock.

  • Graded Potentials and Ion Movement

    • These potentials are either short-lived due to efflux (outflow) and influx (inflow) of ions.

    • Key point: the graded potential must accumulate to reach the threshold for an action potential to occur.

  • Presynaptic Mechanisms

    • The presynaptic membrane contains a specialized pump known as a reuptake pump or reuptake protein, responsible for transporting neurotransmitters from the synaptic cleft back into the presynaptic neuron, aiding in homeostasis and conservation of resources.

    • This process prevents wastage of neurotransmitters and contributes to maintaining effective synaptic transmission.

  • Fate of Neurotransmitters

    • Neurotransmitters can:

    • Diffuse away from the synapse due to concentration gradients (moving from high to low concentrations).

    • Bind to receptor sites, continuing influence on postsynaptic neurons.

    • Be broken down by enzymes specific to that neurotransmitter (e.g., acetylcholine broken down by acetylcholinesterase (ACE)).

    • Taken in by astrocytes that also regulate ion concentrations in the extracellular space.

  • Calcium and Exocytosis

    • The action potential in the presynaptic neuron leads to the opening of voltage-gated calcium channels, allowing calcium ions to flow into the axon terminal.

    • This influx causes exocytosis, the process where neurotransmitter-filled vesicles fuse with the presynaptic membrane to release their contents.

  • SNARE Proteins in Synaptic Function

    • SNARE Proteins include v-SNAREs (e.g., synaptobrevin) and t-SNAREs (e.g., syntaxin and SNAP-25), which interact to facilitate the merging of vesicles with the cell membrane.

    • Once calcium binds to the receptor protein synaptotagmin, it initiates a conformational change that triggers the SNARE protein interaction, leading to vesicle fusion.

  • Action of Calcium

    • Calcium binds to synaptotagmin, subsequently influencing the coil and merge action of the v-SNARE and t-SNARE proteins.

    • This zipper-like action effectively pulls the membranes of the vesicle and presynaptic terminal together, eventually leading to neurotransmitter release into the synapse.

  • Neurotransmitter Reuptake and Implications

    • After release, neurotransmitters act until they are taken back, broken down, or diffused away. For instance,

    • Selective Serotonin Reuptake Inhibitors (SSRIs): Work by blocking serotonin reuptake, enhancing mood.

    • Medications like Adderall primarily enhance dopamine action but can lead to side effects like increased heart rate and anxiety.

  • Latched Potentials Overview

    • Phase 1: Resting State of the Postsynaptic Cell

      • The voltage-gated potassium channel's activation gate is closed but the inactivation gate remains open.

    • Repolarization occurs after depolarization, leading to a return toward the resting state

      • There is a slight undershoot or hyperpolarization due to extended opening of the potassium channels, leading to the refractory period after an action potential.

    • Absolute Refractory Period: No stimulus can result in another depolarization.

    • Relative Refractory Period: A stronger stimulus can trigger depolarization during this time window. Explanations suggest that hyperpolarization requires significantly stronger stimuli.

  • Graded Muscle Responses and Signal Transmission

    • Continuous Conduction vs. Saltatory Conduction:

    • Saltatory conduction, due to myelination, allows action potentials to jump between nodes of Ranvier, leading to faster signal transmission compared to unmyelinated fibers.

    • Implication of conduction velocity influenced by axon diameter and myelination.

    • Group A fibers are large and myelinated, allowing for rapid conduction; Group C fibers are small and unmyelinated, leading to slower transmission.

  • Influences of Ion Concentration and Electrolyte Problems

    • Hyperkalemia: Elevated extracellular potassium levels that reduce the concentration gradient, causing depolarization and increased excitability of cells.

    • Hypokalemia: Low potassium leading to hyperpolarization, resulting in muscle weakness and fatigue.

    • Hyponatremia and Hypernatremia: Affect sodium levels, influencing cell excitability but primarily affect resting membrane potential through potassium dynamics.

  • Neurotransmitter Functions

    • Acetylcholine (ACh): Used in both central and peripheral nervous systems, it can have excitatory or inhibitory effects depending on the receptor type.

    • ACh binding leads to direct channel opening in skeletal muscle and influences cardiac muscle mechanisms preventing excessive heart rate increases.

    • Nicotinic receptors in skeletal muscles are directly responsible for contraction, whereas different receptors determine outcomes in cardiac muscle.

  • Conclusion on Neurotransmitter Role

    • Neurotransmitters act as localized chemical messengers crucial for neuron communication at synapses, determining the functional outcomes based on specific receptor interactions.

Summary Concepts

  • Sodium-Potassium Pump: Maintains ion gradient essential for action potentials by actively transporting 3 Na out per 2 K in.

  • Action Potentials: Represent a rapid reversal of membrane potentials, characterized by phases of depolarization and repolarization.

  • Myelination: Increases the efficiency of neuron signaling and speeds up action potentials, critical for the autonomic nervous system functions.

  • Refractory Periods: Essential for ensuring unidirectional propagation of action potentials and allowing recovery time for neurons.

  • Effects of Neurotransmitter Dynamics: Highlight the complexities of neuropharmacology and implications for drug therapy in treating neurological and psychological disorders.