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96 Terms

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enzyme converting ATP to cAMP

adenylyl cyclase

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small hydrophilic molecule

cAMP

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enzyme that breaks down cAMP into AMP through a hydrolysis reaction

cAMP phosphodiesterase

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serine/threonine kinase regulates metabolic processes in cells and dependent on levels of cAMP in cell

cAMP dependent protein kinase

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Binding of a signaling molecule GPCR on the cell membrane

Step 1 in cAMP signaling pathway

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Activation of a G protein that stimulates adenylyl cyclase

Step 2 of cAMP signaling pathway

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Leading to production of cAMP from ATP

Step 3 of cAMP signaling pathway

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Activation of protein kinase A

Step 4 of cAMP signaling pathway

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PKA phosphorylates target proteins to elicit cellular responses

Steps 5 of cAMP signaling pathway

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Receptor, Activates cAMP and PKC, increases HR, stimulates energy production

Gs

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Inhibitory, inhibits several signaling adenylyl cyclase, decrease heart rate, inhibits neurotransmitter release

Gi

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the Gq protein pathway activates PLC, leading to the breakdown of PIP2 into IP3 and DAG. These products significantly affect cellular behavior by increasing intracellular calcium levels and activating PKC, ultimately resulting in a wide range of physiological responses such as contraction, secretion, growth, and survival.

gq system of g proteins leads to the activation of phospholipase c, the breakdown of pip2. Products of pip2 breakdown affect cellular behavior

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as a response to hormones and transmitters, by a net influx of calcium ions into the cell

Ways in which intracellular Ca2+ concentration can increase

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A rise in intracellular calcium concentration leads to binding of calcium ions to calmodulin, which binds and activates CaMKI I. Upon activation, this enzyme has the ability to autophosphorylate, a process that confers calcium-independent activity upon the kinase and greatly increases its affinity for calmodulin

an increase in cytosolic Ca2+ that alter cellular function through the activity of calmodulin-dependent protein kinases

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  • Diffusion

  • Enzymatic degradation

  • Reuptake

  • Endocytosis

  • Competitive inhibition

  • Conformational changes

Ways that first messengers can be unbound from the receptor

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Sodium

major positive ions extracellular

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Chloride

Major negative ions extracellular

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Potassium

Major positive ions intracellular

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Phosphorous

Major negative ions intracellular

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Opposite charges, such as a positive charge and a negative charge

Attractive

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Like charges, two negative charges or two positive charges, will repel each other.

Repulsive

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separated electrical charges of opposite sign have the potential to do work if they are allowed to come together

Electrical potential

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Determined by the difference in the amount of charge between two points

Potential Difference

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pull the sodium and chlorine ions apart so they are floating freely. These ions are what carry electricity through water, as these charged particles can freely move.

Why is water a good conductor of electricity

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the electrical potential difference across a plasma membrane of an unstimulated cell

resting membrane potential

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K+ that leaks from the inside of the cell to the outside via leak K+ channels and generates a negative charge in the inside of the membrane vs the outside

Why resting membrane potential exists

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when the ion channel opens, the ion moves down its concentration gradient from high to low, in this case for K+ from the inside (intracellular region) to the outside (extracellular region).

Ion distribution across a neuronal membrane

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potassium

Ion contribute most to the resting membrane potential

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maintenance of electrochemical gradients across cell membranes by transporting three Na+ out of and two K+ into cells.

role of the Na+/K+-ATPase in ion distribution across the axonal membrane

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determines the direction that ions will flow through an open ion channel

Electrochemical Gradient

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The electrical potential difference across the cell membrane that exactly balances the concentration gradient for an ion

equilibrium potential

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generates a negative charge in the inside of the membrane vs the outside.

How Na+ leak channels and K+ leak channels contribute to generation of the resting membrane potential

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helps to maintain osmotic equilibrium and membrane potential in cells. The sodium and potassium move against the concentration gradients. The Na+ K+-ATPase pump maintains the gradient of a higher concentration of sodium extracellularly and a higher level of potassium intracellularly.

Role of the Na+/K+-ATPase in MAINTAINING the resting membrane potential despite the presence of leak channels

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action potential in a presynaptic neuron increases the probability of an action potential occurring in a postsynaptic cell.

Excitatory Synapse

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prevents hyperexcitability by providing activity-dependent inhibition.

Inhibitory Synapse

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involves multiple neurons or neuronal cell types providing input onto a common postsynaptic partner,

Convergence

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entails the distribution of synapses from an individual neuron onto multiple postsynaptic partners or partner types.

Divergence

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the nerve impulse is transmitted chemically via neurotransmitters

chemical synapse

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nerve impulse is transmitted electrically via channel proteins.

electrical synapse

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term image

chemical synapse

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Action Potential Arrival: The action potential travels down the axon of the presynaptic neuron and reaches the axon terminal.

Calcium Influx: The depolarization caused by the action potential opens voltage-gated calcium (Ca²⁺) channels in the presynaptic membrane. Calcium ions flow into the neuron.

Neurotransmitter Release: The influx of calcium triggers synaptic vesicles filled with neurotransmitters to move toward and fuse with the presynaptic membrane, releasing their contents into the synaptic cleft through exocytosis.

Neurotransmitter Binding: The released neurotransmitters diffuse across the synaptic cleft and bind to specific receptors on the postsynaptic neuron's membrane.

Postsynaptic Potential Generation: The binding of neurotransmitters to receptors can cause ion channels to open or close, leading to changes in the postsynaptic neuron's membrane potential. This can result in excitatory postsynaptic potentials (EPSPs) or inhibitory postsynaptic potentials (IPSPs).

Integration of Signals: If the excitatory inputs are strong enough to depolarize the postsynaptic neuron to a threshold level, it will generate its own action potential.

Termination of Signal: The neurotransmitter's action is terminated through reuptake into the presynaptic neuron, enzymatic degradation, or diffusion away from the synaptic cleft.

Recycling of Components: The presynaptic neuron can recycle neurotransmitter molecules and vesicular components for future use.

Transmission of a action potential from pre to post synaptic neuron

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These proteins facilitate the docking and fusion of synaptic vesicles with the presynaptic membrane, while these act as calcium sensors that trigger the final release of neurotransmitters in response to calcium influx. Together, these proteins are essential for efficient synaptic transmission and communication between neurons.

SNARE proteins and synaptopgamins in synaptic transmission

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mediate fast synaptic responses by directly controlling ion flow

Ionotropic Receptor

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activate intracellular signaling pathways, leading to slower and more diverse cellular effects

Metabotropic Receptor

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ensures that neurotransmitter signals are brief and that neuronal communication remains flexible and responsive to changing conditions

Neurotransmitter binding to the receptors is transient

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as the number of unbound neurotransmitters decreases, the number of neurotransmitters bound to receptors also decreases, leading to reduced postsynaptic signaling.

NT bound to receptors

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reuptake by the presynaptic neuron, enzymatic degradation in the synaptic cleft, diffusion away from the cleft, and uptake by glial cells

unbound neurotransmitters removed from synaptic cleft

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excitatory neurotransmitters promote depolarization of postsynaptic neurons, generating excitatory postsynaptic potentials (EPSPs) that increase the likelihood of action potential firing

effect of NT’s on excitatory post synaptic neurons

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function to promote depolarization in postsynaptic neurons, increasing their likelihood of firing action potentials. Sodium (Na⁺) and calcium (Ca²⁺) ions flow into the postsynaptic neuron, leading to this depolarization. As graded potentials, EPSPs can vary in magnitude and can summate to determine the overall excitability of the neuron.

excitatory and post synaptic potentials and ions responsible for the direction of flow

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inhibitory synapses and IPSPs function to reduce the excitability of postsynaptic neurons, making it less likely for them to fire action potentials. Chloride (Cl⁻) and potassium (K⁺) ions are primarily responsible for these inhibitory effects, with Cl⁻ flowing into the neuron and K⁺ flowing out. As graded potentials, IPSPs can vary in magnitude and interact with other postsynaptic potentials to modulate neuronal activity.

inhibitory synapses and post synaptic potentials and ions responsible for direction of flow

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rapid succession of inputs from a single source to build a stronger signal

temporal summation

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integrates signals from multiple sources simultaneously

spatial summation

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postsynaptic neuron will fire an action potential or remain resting.

outcome of of spatial and temporal summative events

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integration point for synaptic inputs, its high density of voltage-gated sodium channels, and its ability to determine whether the membrane potential reaches the threshold needed to initiate an action potential.

importance of axon hillock generating action potentials

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high density of voltage-gated sodium channels, specific membrane properties, efficient integration of synaptic inputs, and its role in action potential generation.

threshold potential is lower at the axon hillock

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responsible for fast communication between neurons

neurotransmitter

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adjust and fine-tune that communication over a longer duration, influencing a broader range of neural activity

neuromodulator

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Amino acids, biogenic amines, neuropeptides, purines, gasotransmitters, acetylcholine

classes of neurotransmitters and neuromodulators

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involves the combination of acetyl-CoA and choline, catalyzed by choline acetyltransferase. The resulting ACh is then stored in synaptic vesicles until released into the synaptic cleft, where it can bind to receptors on the postsynaptic cell, facilitating neurotransmission.

acetylcholine synthesis

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crucial role in terminating the action of acetylcholine in synapses, ensuring that signals are brief and well-regulated. AChE inhibitors increase the duration of ACh action, enhancing synaptic transmission but also carrying the risk of overstimulation and toxicity.

Function of acetylcholinesterase

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ACh receptor that primarily mediate fast synaptic transmission and muscle contraction,

Nicotinic receptor

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ACh receptor involved in slower, modulatory actions within the autonomic nervous system and the brain.

Muscarinic Receptor

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Dopamine, Norepinephrine, Adrenaline

NT’s that are catecholamines

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crucial for the degradation of monoamines, regulating their levels in the synapse. These inhibitors enhance neurotransmission by preventing the breakdown of these neurotransmitters, leading to increased synaptic levels, which can have therapeutic effects, particularly in treating depression.

Monoamine oxidase

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Location: Blood vessels, CNS, smooth muscle, organs

Mode of Action

GPCRs (Gq protein) for a-1; inhibitory for a-2

Subtypes

A-1, A-2

Effectors

Vasoconstriction, inhibition of neurotransmitter release (a-2)

Alpha Adrenergic Receptor

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Location

Heart, lungs, smooth muscle, adipose tissue

Mode of Action

GPCRs (Gs protein)

Subtypes

Beta-1, Beta-2, Beta-3

Effectors

Increased heart rate (beta-1), bronchodilation (beta-2), lipolysis (beta-3)

Beta-adrenergic Receptor

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crucial for modulating a variety of physiological functions in the nervous system, including pain regulation, mood modulation, and homeostasis. Examples include substance P, which is primarily associated with pain transmission, and endorphins, which help manage pain and promote feelings of pleasure.

neuropeptides

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  • General Function: Prepares the body for "fight or flight" responses during stressful situations.

  • Effects:

    • Increases heart rate and blood pressure.

    • Dilates airways to improve breathing.

    • Inhibits digestive processes.

    • Mobilizes energy stores by stimulating glucose release from the liver.

    • Increases blood flow to skeletal muscles while reducing flow to non-essential organs.

Sympathetic Nervous System

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  • General Function: Promotes "rest and digest" activities, conserving energy and maintaining homeostasis during calm situations.

  • Effects:

    • Decreases heart rate and blood pressure.

    • Constricts airways.

    • Stimulates digestive processes, including saliva production and peristalsis.

    • Promotes nutrient absorption and storage.

    • Increases blood flow to digestive organs.

Parasympathetic Nervous System

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consists of preganglionic neurons originating from the CNS, autonomic ganglia where synapses occur, and postganglionic neurons that innervate target organs. The sympathetic division promotes widespread responses, while the parasympathetic division facilitates more localized control.

Anatomical organization of autonomic motor system

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both divisions of the ANS utilize ACh in their preganglionic neurons, but they differ significantly in the neurotransmitters used by postganglionic neurons and the resulting physiological effects. But this division prepares the body for action, while the parasympathetic division promotes relaxation and recovery.

preganglionic and postganglionic neurons

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contains only one neuron because it functions as a specialized structure that directly releases hormones into circulation, bypassing the need for an intermediate postganglionic neuron.

sympathetic pathway to the adrenal medulla

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release of epinephrine and norepinephrine plays a critical role in the body’s response to stress, enabling rapid physiological adjustments to prepare for immediate physical demands. These hormones work synergistically to enhance alertness, energy availability, and physical performance during stressful situations.

chemicals released from adrenal medulla

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key feature of the ANS that allows for intricate control of various bodily functions, enabling the body to respond appropriately to different situations. This interplay between the sympathetic and parasympathetic divisions ensures that organs can be activated or inhibited as needed, contributing to overall physiological balance and homeostasis.

Dual Innervation

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key electrical change in cells that initiates processes like action potentials in neurons and contractions in muscle cells.

Depolarize

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process of restoring a cell's resting membrane potential after depolarization.

Repolarize

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cell's membrane potential becomes more negative than its resting state, making it less likely to fire an action potential.

Hyperpolarize

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occurs when positively charged sodium ions enter the cell, causing the inside of the cell to become less negatively charged (more positive). This process is crucial for the generation of action potentials in neurons and muscle cells, enabling them to communicate and function effectively.

Depolarization of the membrane

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stronger stimuli lead to larger graded potentials. This relationship allows cells to encode the intensity of stimuli, which is crucial for processes such as sensory perception and neuronal signaling.

relationship between strength of graded potential and strength of stimulus

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diminishes over distance due to factors such as current leakage and the resistance of the cell membrane.

strength of a graded potential

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through temporal and spatial mechanisms, significantly affects the strength of graded potentials. This process enhances the ability of neurons to respond to varying intensities and frequencies of input, ultimately influencing whether or not an action potential will be generated.

summation of multiple stimuli

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Skeletal, Cardiac, Smooth, Neurons, Endocrine Cells, Sensory Cells are crucial for transmitting signals and facilitating responses to stimuli throughout the body.

Cells that have excitable membranes

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involves a series of well-coordinated events: depolarization (Na⁺ influx), repolarization (K⁺ efflux), and often hyperpolarization. These rapid changes in membrane potential allow for the transmission of signals along neurons and muscle fibers, making action potentials fundamental to nervous system and muscle function.

Events occurring in an action potential

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Local changes in membrane potential

Magnitude

Varies with stimulus strength

Duration

Longer-lasting (milliseconds to seconds)

Propagation

Local, diminishes with distance

Threshold Requirement

No threshold required

Summation

Can summate (temporal and spatial)

Types

Can be excitatory or inhibitory

Graded Potentials

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Rapid, all-or-nothing changes in membrane potential

Magnitude

Fixed magnitude (same for each action potential)

Duration

Short-lived (1-2 milliseconds)

Propagation

Propagates without decrement

Threshold Requirement

Requires reaching a specific threshold

Summation

Does not summate; all-or-nothing response

Types

Always excitatory

Action Potentials

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Respond to chemical signals, leading to localized changes in membrane potential.

Ligand-Gated Ion Channels in changing membrane voltage

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Respond to changes in membrane voltage, crucial for the propagation of action potentials.

Voltage-Gated Ion Channels in changing membrane voltage

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Respond to mechanical stimuli, allowing cells to detect and respond to physical changes in their environment.

Mechanically-Gated Ion Channels in changing membrane voltage

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  • Depolarization: Initiated by the rapid opening of voltage-gated sodium channels, allowing Na⁺ influx.

  • Repolarization: Caused by the closing of sodium channels and the opening of voltage-gated potassium channels, leading to K⁺ efflux.

  • Afterhyperpolarization: Continued K⁺ outflow results in a temporary hyperpolarized state.

  • Return to Resting State: Sodium-potassium pumps help restore ion concentrations and stabilize the membrane potential.

Ion channels initiate and end of an action potential

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membrane voltage level that must be achieved for an action potential to be initiated, marking a crucial point in the excitability of neurons and muscle cells. It underpins the all-or-nothing principle of action potentials, ensuring that a sufficient stimulus leads to a full-scale electrical response.

Threshold potential

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asserts that once the threshold is reached, an action potential is generated with a consistent amplitude and duration.

All-or-none law of action potential

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No action potential can occur, primarily due to inactivated Na⁺ channels; lasts for about 1-2 milliseconds.

Absolute Refractory Period

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A stronger-than-normal stimulus can generate an action potential, influenced by the partial recovery of Na⁺ channels and ongoing K⁺ efflux; lasts for about 2-4 milliseconds.

Relative Refractory Period

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Conduct action potentials through continuous conduction, with sequential depolarization along the entire length of the axon, resulting in slower signal transmission (1-10 m/s)

Action potentials in unmyelinated axons

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Conduct action potentials through saltatory conduction, where the action potential jumps between Nodes of Ranvier, allowing for much faster signal transmission (up to 120 m/s).

Action potentials in myelinated axons

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term image

Action Potential