Premed · Premed · Anatomy Physiology 1
Lecture 14: The Action Potential and Synaptic Transmission
Anatomy and Physiology I
Learning Objectives
By the end of this lecture, students will be able to:
- Define resting membrane potential and explain its ionic basis
- Describe the role of the sodium-potassium pump in maintaining resting membrane potential
- Define graded potential and describe its properties
- Describe the phases of an action potential
- Explain the concepts of threshold, all-or-none principle, absolute and relative refractory periods
- Compare continuous and saltatory conduction
- Describe the events of synaptic transmission at a chemical synapse
- Distinguish between excitatory and inhibitory postsynaptic potentials
- Explain spatial and temporal summation and synaptic integration
Lecture Content
I. Resting Membrane Potential (RMP)
The resting membrane potential is the voltage difference across the plasma membrane of an unstimulated (resting) neuron, typically approximately -70 mV, meaning the inside is negative relative to the outside. The membrane is said to be polarized at rest.
Ionic Basis of the RMP
The resting membrane potential arises from the unequal distribution of ions across the membrane. K+ is at high concentration inside the cell and low outside. Na+ is at high concentration outside the cell and low inside. Cl- is high outside. Large intracellular anions (A-), including proteins and other organic molecules, are trapped inside the cell and cannot cross the membrane.
At rest, the membrane is much more permeable to K+ than to Na+ (approximately 50 to 100 times more permeable) because K+ leak channels are far more numerous than Na+ leak channels. As a result, K+ diffuses out of the cell down its concentration gradient, leaving behind negative charges (anions) and creating a net negative charge inside — the resting membrane potential. Some Na+ leaks in, slightly offsetting the negative charge.
The Sodium-Potassium Pump (Na+/K+ ATPase)
The sodium-potassium pump actively transports 3 Na+ out and 2 K+ in per ATP hydrolyzed. It maintains the concentration gradients for Na+ and K+ and contributes a small amount of negativity to the RMP because it is an electrogenic pump, exporting more positive charge than it imports. Without the pump, the ionic gradients would eventually dissipate.
II. Graded Potentials
Graded potentials are short-lived, localized changes in membrane potential that vary in magnitude (amplitude). They are triggered by stimuli such as neurotransmitters, sensory stimuli, or mechanical changes. The stronger the stimulus, the larger the graded potential — amplitude is proportional to stimulus strength. Graded potentials are decremental, meaning signal strength decreases with distance from the stimulus as the current dissipates. They can be depolarizing (toward threshold, making the inside less negative) or hyperpolarizing (away from threshold, making the inside more negative).
Examples include receptor potentials in sensory receptors, postsynaptic potentials (EPSPs and IPSPs) at synapses, and end-plate potentials at the neuromuscular junction. Graded potentials serve as the triggers for action potentials: if a graded potential at the axon hillock reaches threshold, an action potential is generated.
III. The Action Potential (AP)
An action potential is a brief, large, all-or-none reversal of membrane potential that propagates along the axon. It is generated only if the membrane is depolarized to threshold (approximately -55 mV). The principal ions involved are Na+ and K+, and the process is mediated by voltage-gated ion channels.
Phases of the Action Potential
The action potential proceeds through four phases. In the resting state, all voltage-gated Na+ and K+ channels are closed and the membrane is at -70 mV.
During the depolarization phase, a stimulus depolarizes the membrane to threshold (-55 mV). Voltage-gated Na+ channels open rapidly as their activation gates open, and Na+ rushes into the cell down its electrochemical gradient. The membrane rapidly depolarizes, becoming positive and reaching approximately +30 mV. This process involves positive feedback: depolarization opens more Na+ channels, which causes further depolarization.
During the repolarization phase, voltage-gated Na+ channels inactivate as their inactivation gates close, stopping Na+ influx. Voltage-gated K+ channels, which are slower to respond (delayed rectifiers), open, and K+ rushes out of the cell, restoring the negative membrane potential. The membrane returns toward -70 mV.
During hyperpolarization (undershoot), the membrane potential briefly dips below -70 mV to approximately -75 to -80 mV because K+ channels are slow to close and excess K+ exits before the channels fully close. The membrane then returns to resting potential as K+ channels close and the Na+/K+ pump restores ionic balance.
<image>A graph of an action potential plotted as membrane potential (mV, y-axis) versus time (ms, x-axis). The tracing starts at the resting membrane potential of -70 mV. A dotted line marks the threshold at -55 mV. The depolarization phase shows a rapid rise from -70 mV to +30 mV (labeled "Na+ channels open, Na+ influx"). The peak is at +30 mV. The repolarization phase shows a return toward -70 mV (labeled "Na+ channels inactivate, K+ channels open, K+ efflux"). A brief hyperpolarization dip to approximately -80 mV is shown (labeled "K+ channels slow to close"). The trace returns to -70 mV. Alongside the graph, the states of voltage-gated Na+ channels (closed, open, inactivated, closed) and K+ channels (closed, closed, open, closed) are illustrated at each phase.</image>
IV. Key Properties of the Action Potential
All-or-None Principle
A neuron either fires a complete action potential or does not fire at all. Once threshold is reached, the AP runs to completion regardless of stimulus strength. Stronger stimuli do NOT produce larger action potentials; instead, they increase the frequency of action potentials.
Threshold
Threshold is the critical level of depolarization (approximately -55 mV) that must be reached to trigger an AP. Subthreshold stimuli do not produce APs, while threshold and suprathreshold stimuli do.
Refractory Periods
The absolute refractory period is the time during which no stimulus, no matter how strong, can trigger a second AP. It corresponds to the period when Na+ channels are open or inactivated. The absolute refractory period ensures one-way propagation of the AP (preventing it from traveling backward) and sets the upper limit on firing frequency. The relative refractory period is the period during which a second AP can be generated, but only by a stronger-than-normal (suprathreshold) stimulus. It corresponds to the period when K+ channels are still open and the membrane is hyperpolarized; a stronger stimulus can overcome the increased K+ efflux.
V. Propagation of the Action Potential
Once generated at the axon hillock, the AP propagates along the axon to the terminals. The depolarized region generates local currents that depolarize adjacent membrane to threshold, generating a new AP at the adjacent region. The AP does not decrease in amplitude as it travels, unlike a graded potential.
Continuous Conduction (Unmyelinated Axons)
In continuous conduction, the AP propagates sequentially along every patch of membrane. This mode is slower (0.5 to 2 m/s for small unmyelinated fibers) and requires more energy because more ion channels open and close along the entire axon.
Saltatory Conduction (Myelinated Axons)
In saltatory conduction, myelin insulates the axon between nodes, and current can only flow at the nodes of Ranvier, where voltage-gated channels are concentrated. The AP effectively "jumps" from node to node. This mode is much faster (up to 130 m/s for large myelinated fibers) and more energy-efficient because fewer ions cross the membrane, reducing the work required of the Na+/K+ pump.
Factors Affecting Conduction Speed
Three factors influence conduction speed. Axon diameter plays a role because a larger diameter means less resistance and faster conduction. Myelination dramatically increases speed; myelinated axons conduct much faster than unmyelinated axons of the same diameter. Temperature also affects speed, with higher temperatures increasing conduction speed up to a limit.
<image>A diagram comparing continuous and saltatory conduction. Panel A (Continuous conduction): An unmyelinated axon with sequential depolarization shown as positive charges inside the membrane spreading to adjacent regions, with each small segment undergoing its own action potential. Arrows show slow, step-by-step propagation. Panel B (Saltatory conduction): A myelinated axon with Schwann cells covering internodal segments and nodes of Ranvier exposed. The action potential jumps from node to node, with current flowing through the myelinated segments as local circuit currents (shown as arrows inside the axon). The AP is regenerated only at the nodes. A speed comparison shows 0.5-2 m/s for unmyelinated versus up to 130 m/s for large myelinated fibers.</image>
VI. Synaptic Transmission
Types of Synapses
Electrical synapses use gap junctions that directly connect the cytoplasm of adjacent cells, allowing ions to flow through directly. They are very fast and are found in cardiac muscle, smooth muscle, and some brain regions, where they enable synchronous activity. Chemical synapses are the most common type in the nervous system. They use neurotransmitters to transmit signals across a synaptic cleft. Although slower than electrical synapses, they allow signal modification and integration.
Structure of a Chemical Synapse
A chemical synapse consists of three components. The presynaptic neuron sends the signal; its axon terminal contains synaptic vesicles loaded with neurotransmitter. The synaptic cleft is a narrow gap of 20 to 50 nanometers between the presynaptic and postsynaptic membranes. The postsynaptic neuron (or effector cell) receives the signal, and its membrane contains receptors for the neurotransmitter.
Events of Chemical Synaptic Transmission
The sequence of chemical synaptic transmission proceeds as follows. An action potential arrives at the axon terminal of the presynaptic neuron. Depolarization opens voltage-gated Ca2+ channels at the terminal, and Ca2+ enters, triggering exocytosis of synaptic vesicles. Neurotransmitter is released into the synaptic cleft, diffuses across, and binds to receptors on the postsynaptic membrane. This binding opens (or closes) ion channels on the postsynaptic membrane, producing a postsynaptic potential. The neurotransmitter is then rapidly removed from the cleft by one of several mechanisms: enzymatic degradation (such as AChE breaking down ACh), reuptake into the presynaptic terminal (as occurs with serotonin, norepinephrine, and dopamine), diffusion away from the cleft, or uptake by astrocytes (as occurs with glutamate).
VII. Postsynaptic Potentials
Excitatory Postsynaptic Potential (EPSP)
An EPSP is a depolarizing graded potential that moves the postsynaptic membrane toward threshold. It is caused by the opening of channels permeable to Na+ (and sometimes K+ and Ca2+), resulting in net Na+ influx. An EPSP makes an action potential MORE likely. Examples of excitatory neurotransmitters include glutamate and acetylcholine (at nicotinic receptors).
Inhibitory Postsynaptic Potential (IPSP)
An IPSP is a hyperpolarizing graded potential that moves the postsynaptic membrane away from threshold. It is caused by the opening of K+ channels (allowing K+ efflux) or Cl- channels (allowing Cl- influx). An IPSP makes an action potential LESS likely. Examples of inhibitory neurotransmitters include GABA and glycine.
VIII. Synaptic Integration
A single EPSP is rarely sufficient to bring the postsynaptic neuron to threshold. The postsynaptic neuron integrates (sums) inputs from many presynaptic neurons.
Temporal Summation
In temporal summation, rapid, successive EPSPs from the same presynaptic neuron are added together. If stimuli arrive before the previous EPSP has decayed, the EPSPs summate and can bring the membrane to threshold, triggering an AP.
Spatial Summation
In spatial summation, EPSPs (or IPSPs) from different presynaptic neurons arriving simultaneously are added together at the axon hillock. Multiple simultaneous EPSPs can summate to reach threshold.
Integration at the Axon Hillock
The axon hillock is the trigger zone for action potential generation because it has the lowest threshold, owing to the highest density of voltage-gated Na+ channels. The net effect of all EPSPs and IPSPs arriving at any given moment determines whether the neuron fires. If the sum of all inputs depolarizes the axon hillock to threshold, an AP is generated. If IPSPs offset the EPSPs sufficiently, no AP is produced.
IX. Neurotransmitters (Overview)
Acetylcholine (ACh) is excitatory at the NMJ and excitatory or inhibitory in the CNS and ANS, depending on the receptor type. Among the amino acid neurotransmitters, glutamate is the main excitatory neurotransmitter in the CNS, GABA (gamma-aminobutyric acid) is the main inhibitory neurotransmitter in the brain, and glycine is the main inhibitory neurotransmitter in the spinal cord.
The biogenic amines (monoamines) include norepinephrine (NE), which functions in the sympathetic ANS and promotes alertness and arousal; dopamine, which is involved in motor control, reward, pleasure, and motivation; serotonin (5-HT), which modulates mood, sleep, appetite, and pain; and histamine, which contributes to wakefulness and gastric acid secretion.
Neuropeptides are larger molecules often co-released with other neurotransmitters. They include endorphins and enkephalins, which are natural painkillers that bind to opioid receptors, and substance P, which is involved in pain signaling. Purines such as ATP and adenosine serve neuromodulatory roles. Gases such as nitric oxide (NO) act as retrograde messengers and cause vasodilation.
<image>A step-by-step diagram of chemical synaptic transmission. A presynaptic axon terminal is shown at the top, with labeled mitochondria and synaptic vesicles containing neurotransmitter molecules. The synaptic cleft is in the middle. The postsynaptic membrane is at the bottom with receptor proteins and ion channels. Numbered steps show: (1) AP arrives at the terminal, (2) voltage-gated Ca2+ channels open and Ca2+ enters, (3) Ca2+ triggers vesicle fusion and neurotransmitter release into the cleft, (4) neurotransmitter binds to postsynaptic receptors, (5a) ion channels open producing an EPSP (shown with Na+ entering), or (5b) ion channels open producing an IPSP (shown with Cl- entering or K+ leaving), (6) neurotransmitter removal by enzymatic degradation, reuptake, or diffusion. An inset shows temporal summation (repeated EPSPs from one source adding up) and spatial summation (simultaneous EPSPs from multiple sources adding up at the axon hillock).</image>
