Neuronal excitability Flashcards

1
Q

What is subcellular polarity in neurons?

A

Neurons have directional polarity where inputs are received at dendrites (somadendritic compartment) and outputs are transmitted at the axon (axonal compartment). The action potential is generated at the axon initial segment (AIS) and propagated toward the synapse.

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2
Q

Why is the axon initial segment important for action potentials?

A

The AIS has the highest density of sodium channels, making it the site where action potentials are initiated due to the low threshold for sodium channel activation. Its location and density of channels determine how easily and where an action potential starts.

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3
Q

What is the role of Nodes of Ranvier in action potential propagation?

A

The Nodes of Ranvier contain high densities of voltage-gated sodium channels that allow for the regeneration of the action potential as it travels down the axon. This helps with saltatory conduction, making signal transmission faster and more efficient.

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4
Q

What is the general structure of voltage-gated ion channels?

A

Voltage-gated ion channels consist of four subunits (tetramers) with 6 transmembrane domains each. The 4th transmembrane domain (S4) is positively charged and acts as a voltage sensor, moving in response to changes in membrane potential.

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5
Q

Q: What are the differences between fast and slow inactivation of voltage-gated channels?

A

A: Fast inactivation occurs in channels like sodium channels, allowing them to close quickly after activation to enable rapid firing of action potentials. Slow inactivation, often seen in some calcium and potassium channels, modulates prolonged neuronal activity and helps in signal integration.

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6
Q

Q: What toxins/pharmacological agents block sodium channels, and why is this important?

A

A: Sodium channels can be blocked by toxins such as tetrodotoxin (TTX) and saxitoxin (STX) from outside the cell, and by intracellular agents like QX-314. These blockers are crucial for understanding and isolating sodium channel function in experiments.

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7
Q

Q: Why is potassium channel diversity important in neurons?

A

A: Potassium channels have varied inactivation rates (fast, slow, or none), which regulate neuronal excitability. For example, high inactivation channels delay action potential firing, while delayed rectifier channels help repolarize the membrane after an action potential.

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8
Q

Q: What did the Nobel Prize-winning patch-clamp technique reveal about ion channels?

A

A: The patch-clamp technique allowed researchers to record ion currents through individual channels, revealing that channel opening is stochastic (probabilistic) rather than deterministic, providing insight into how channels contribute to overall neuronal activity.

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9
Q

Q: How does the probabilistic model explain sodium channel behavior?

A

A: Sodium channels have a high probability of opening at the beginning of depolarization, but this probability decreases over time. Depolarization increases the likelihood of channels opening but does not guarantee that every channel will open.

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10
Q

Q: What is the relationship between resting potential, threshold, and action potential in a neuron?

A

Resting potential is the stable negative charge of a neuron’s membrane when not active, typically around -70mV. This is maintained by the sodium-potassium pump and selective ion permeability.

Threshold is the critical membrane potential, about -55mV, that a neuron must reach through depolarization to trigger an action potential. This threshold is crossed when excitatory inputs sufficiently depolarize the membrane.

Action potential occurs once the threshold is met. Voltage-gated sodium (Na⁺) channels open, causing a rapid influx of Na⁺, depolarizing the membrane to around +30mV. This is followed by the opening of potassium (K⁺) channels, repolarizing the cell.

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11
Q

Q: How do sodium and potassium conductances differ during an action potential?

A

A: Sodium channels open rapidly during depolarization, causing the upstroke of the action potential. Potassium channels open more slowly, contributing to repolarization and after-hyperpolarization, preventing immediate reactivation of the neuron.

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12
Q

Q: What are the key phases of an action potential?

A

A: (1) Resting potential, (2) Depolarization (Na+ influx), (3) Repolarization (K+ efflux), (4) Hyperpolarization (excess K+ leaving), and (5) Return to resting potential.

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13
Q

Q: What are inward and outward currents in a neuron?

A

A: Inward currents, primarily carried by Na+ ions, lead to depolarization, while outward currents, usually carried by K+ ions, restore the membrane potential through repolarization and hyperpolarization.

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14
Q

Q: How do IV curves reflect sodium and potassium currents?

A

A: IV curves show the current through ion channels at different membrane potentials. Sodium channels show inward current with depolarization, while potassium channels show outward current with depolarization, each reaching a reversal potential.

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15
Q

Q: What does it mean that channel opening is stochastic?

A

A: Ion channel opening is probabilistic; depolarization increases the probability of channel opening, but it does not guarantee that all channels will open simultaneously. This adds variability to action potential initiation and propagation.

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16
Q

Q: How do calcium channels vary in inactivation?

A

A: Some calcium channels inactivate quickly (e.g., L-type), while others inactivate slowly or not at all. This allows calcium channels to support different neuronal functions, such as synaptic plasticity or sustained firing.

17
Q

Q: How is the axon initial segment (AIS) plastic?

A

A: Recent research shows that the AIS is not static and can change in length or position in response to neuronal activity. This plasticity affects action potential initiation and neuronal excitability.

18
Q

Q: What is the spike initiation zone, and why is it important?

A

A: The spike initiation zone, located at the AIS, has the highest density of sodium channels. It is the first site where an action potential is generated due to the low current threshold required for sodium channel activation.

19
Q

Q: What is the significance of the voltage sensor in ion channels?

A

A: The voltage sensor (S4 domain) is positively charged and moves in response to changes in membrane potential, triggering the conformational change that opens the channel.

20
Q

Q: Why are single-channel recordings essential for understanding neuronal excitability?

A

A: Single-channel recordings provide direct insights into how individual ion channels contribute to overall ionic currents and action potentials, allowing for a better understanding of neuronal signaling at the microscopic level.

21
Q

Q: Why is subcellular polarity crucial for neuronal function?

A

A: Polarity ensures that neurons can efficiently receive, integrate, and transmit signals. Dendrites are optimized for receiving inputs, while axons specialize in signal output, ensuring clear directional flow of information.

22
Q

Q: How does AIS plasticity influence neural computation?

A

A: Changes in AIS length or position can alter the threshold for action potential initiation, thus affecting the timing of spikes, which is crucial for processes like learning, adaptation, and synaptic integration.

23
Q

Q: How does the stochastic nature of sodium channel opening affect action potential generation?

A

A: The probabilistic opening of sodium channels means that not every depolarization will trigger an action potential. This introduces variability in neuronal firing, which can be important for neural coding and signal processing.

24
Q

Q: Why is the distinction between fast and slow inactivation important for neuronal signaling?

A

A: Fast inactivation allows neurons to fire rapid bursts of action potentials, while slow inactivation modulates longer-lasting processes like synaptic plasticity or sustained firing, both critical for different types of neural communication.

25
Q

Q: What are the experimental implications of using voltage-gated channel blockers?

A

A: By selectively blocking channels like sodium or potassium, researchers can isolate specific currents and understand their role in action potential generation and