Neurophysiology Chapter: Action Potential
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What two ions are primarily responsible for the action potential, according to Hodgkin and Huxley's research?

Sodium (Na+) and potassium (K+)

What is the significance of the giant axon of squid in Hodgkin and Huxley's experiments?

This axon is large enough to allow for insertion of electrodes to measure electrical activity and study ion movement.

Describe the state of the membrane potential at rest, in terms of sodium and potassium ion permeability.

The membrane potential at rest is negative (-65mV). Potassium permeability is much higher than sodium permeability, contributing to the negative resting potential.

What happens to the permeability of sodium ions during depolarization, and what is the impact on the membrane potential?

<p>Sodium permeability increases rapidly during depolarization. The influx of sodium ions makes the membrane potential more positive, leading to the characteristic spike of the action potential.</p> Signup and view all the answers

Explain how the membrane potential returns to its resting value after depolarization.

<p>The membrane potential returns to resting value due to the opening of potassium channels, allowing potassium ions to flow out of the cell, restoring the negative charge.</p> Signup and view all the answers

What is the main limitation of the simple model of action potential, and how does it relate to the opening and closing of ion channels?

<p>The simple model fails to explain how sodium channels stay closed long enough for potassium channels to repolarize the membrane. This relates to the concept of inactivation of sodium channels, which prevents them from reopening immediately during repolarization.</p> Signup and view all the answers

What is the importance of sodium channel inactivation in the context of the action potential?

<p>Sodium channel inactivation ensures that the membrane can repolarize properly, preventing continuous depolarization and allowing for the next action potential to occur.</p> Signup and view all the answers

In your own words, explain the significance of Hodgkin and Huxley's research in understanding the action potential.

<p>Their research revolutionized our understanding of the action potential by demonstrating the crucial role of sodium and potassium ions in generating nerve impulses. This laid the foundation for understanding how neurons communicate in the nervous system.</p> Signup and view all the answers

Explain how the use of an electrode allows us to measure either the membrane potential (Vm) or the current (Im) flowing across a neuron's membrane.

<p>By using an electrode, we can either impose a current across the membrane and measure the resulting membrane potential (Vm), or we can measure the current (Im) flowing across the membrane while holding the membrane potential at a specific value.</p> Signup and view all the answers

Explain how Ohm's law is applied in cellular electrophysiology to understand the relationship between membrane potential (Vm), current (Im), and membrane resistance (Rm).

<p>Ohm's law states that Vm = Rm x Im, meaning the membrane potential (Vm) is equal to the product of the membrane resistance (Rm) and the current (Im) flowing across the membrane. This describes the relationship between these three variables and provides a framework for understanding the electrical activity of a neuron.</p> Signup and view all the answers

What are the two main approaches to measuring electrical signals in a neuron using an electrode, and what does each approach allow us to determine?

<p>The two approaches are: 1) Imposing a current (Im) and measuring the resulting membrane potential (Vm) This allows us to determine the membrane resistance (Rm) as well as the relationship between current and voltage. 2) Measuring the current (Im) while controlling the membrane potential (Vm) This allows us to determine the specific ion channels that are active at a given membrane potential.</p> Signup and view all the answers

Why is it important to be able to separate the measurement of the membrane potential (Vm) and the current (Im) flowing across a neuron's membrane?

<p>Separating the measurement of Vm and Im allows us to better understand the relationship between these two variables and how they contribute to the overall electrical activity of a neuron. It allows us to study the properties of specific ion channels and how they contribute to the generation and propagation of action potentials.</p> Signup and view all the answers

What are some of the key reasons why we might want to measure the electrical activity of a neuron?

<p>Measuring the electrical activity of a neuron allows us to understand how neurons communicate with each other, how they process information, and how they contribute to the function of the nervous system. This knowledge is essential for understanding brain function and for developing treatments for neurological disorders.</p> Signup and view all the answers

What does the 'TTX' in the initial text refer to?

<p>Tetrodotoxin</p> Signup and view all the answers

Why is the Na+ current (INa) not sustained throughout the depolarization?

<p>The Na+ current (INa) inactivates.</p> Signup and view all the answers

What is the name of the technique used to measure currents through single ion channels?

<p>Patch-clamping</p> Signup and view all the answers

What is the fundamental difference between leak channels and voltage-gated channels?

<p>Leak channels are always open, while voltage-gated channels open and close in response to changes in membrane potential.</p> Signup and view all the answers

What is the state of a voltage-gated channel when its activation gate is closed?

<p>Closed</p> Signup and view all the answers

How many gates are necessary for a channel to pass current?

<p>All gates must be open.</p> Signup and view all the answers

What is the process of opening a closed channel referred to as?

<p>Activation</p> Signup and view all the answers

What is the process of closing an open channel referred to as?

<p>Deactivation</p> Signup and view all the answers

What is the name given to the event that leads to the transition from a closed to an inactivated state?

<p>Inactivation</p> Signup and view all the answers

What is the process known as that returns an inactivated channel back to its closed state?

<p>Recovery from inactivation</p> Signup and view all the answers

What is the name of the voltage-gated channel discussed in this text?

<p>Na+ channel</p> Signup and view all the answers

What does the text suggest about the state of the Na+ channels at -80 mV?

<p>They are closed, i.e. deactivated.</p> Signup and view all the answers

What is the significance of the fact that Na+ channels inactivate during prolonged depolarization?

<p>It prevents the continuous flow of Na+ ions, ensuring that the action potential is brief and does not last indefinitely.</p> Signup and view all the answers

What is the primary difference between a 'voltage-clamp' and a 'current-clamp' experiment?

<p>The key difference lies in the controlled variable. 'Voltage-clamp' experiments fix the membrane potential (Vm) and measure the resulting current (Im), while 'current-clamp' experiments fix the injected current (Ielec) and measure the resulting membrane potential (Vm).</p> Signup and view all the answers

Describe the principle of operation for a voltage-clamp circuit.

<p>A voltage-clamp circuit continuously monitors the membrane potential (Vm) and adjusts the injected current (Ielectrode) to maintain Vm at a predetermined value (Vclamp). This ensures that the membrane potential is kept constant, allowing the researcher to study the underlying ion channels and their behavior.</p> Signup and view all the answers

What is the main advantage of utilizing a voltage-clamp technique to study ion channels compared to current-clamp?

<p>Voltage-clamp provides precise control over membrane potential (Vm), enabling the direct measurement of ion current (Im) at specific voltage values. This allows researchers to analyze the voltage dependence of ion channel activity and identify the specific currents carried by different ions.</p> Signup and view all the answers

From the perspective of a neuron, briefly explain how a voltage-clamp experiment would provide information about an action potential.

<p>A voltage-clamp experiment allows researchers to mimic the depolarization and repolarization phases of an action potential by taking the neuron's membrane potential through different stages. By measuring the resulting current flow, the voltage-clamp technique reveals the underlying ionic basis of the action potential, including the activation and deactivation of sodium and potassium channels.</p> Signup and view all the answers

Why are voltage-clamp experiments valuable for understanding the properties of ion channels?

<p>Voltage-clamp experiments allow researchers to directly measure how ion channels respond to changes in membrane potential (Vm). By isolating the effect of specific voltage changes on ion channel activity, researchers can determine the voltage-dependence of ion channel opening and closing, and identify the specific ions that each channel conducts. This provides valuable information about the role of specific ion channels in neuronal signaling.</p> Signup and view all the answers

How does the 'voltage-clamp' technique help in the study of the Na+ and K+ currents that contribute to an action potential?

<p>Voltage-clamp experiments allow researchers to study the behavior of Na+ and K+ channels by fixing the membrane potential at specific values, such as resting and depolarized states. This allows for the isolation and measurement of the individual currents generated by Na+ and K+ channels, providing insights into their voltage-dependent activation and inactivation during an action potential.</p> Signup and view all the answers

What are the steps involved in a voltage-clamp experiment?

<p>A voltage-clamp experiment begins by injecting a current (Ielectrode) and measuring the resulting membrane potential (Vm). If Vm is different from the desired clamp voltage (Vclamp), the injected current is adjusted until Vm equals Vclamp. This iterative process of measuring and adjusting the current ensures that the membrane potential remains fixed at the targeted value.</p> Signup and view all the answers

Explain the role of the 'clamp' and 'recording' electrodes in a voltage-clamp experiment.

<p>The 'clamp' electrode provides the injected current (Ielectrode) to control the membrane potential, while the 'recording' electrode measures the resulting membrane potential (Vm). The clamp electrode is used to maintain the membrane potential at the desired value, while the recording electrode provides information about the actual voltage across the membrane.</p> Signup and view all the answers

Describe the difference between the roles of sodium and potassium channels in the generation of an action potential.

<p>Sodium channels open quickly during depolarization, causing the rapid rise of the action potential. Potassium channels open more slowly and allow potassium ions to flow out, leading to the repolarization phase.</p> Signup and view all the answers

Explain the concept of the refractory period in the context of action potential generation.

<p>The refractory period is a time after an action potential when the cell is less likely to generate another one. This is due to the inactivation of Na+ channels and the continued outward flow of K+ ions.</p> Signup and view all the answers

What is the significance of the axon hillock in the initiation of action potentials in neurons?

<p>The axon hillock is the region of the neuron where the axon emerges from the cell body. It has a high density of voltage-gated sodium channels, making it the site where action potentials are typically initiated.</p> Signup and view all the answers

How does the presence of myelin affect the speed of action potential propagation?

<p>Myelin acts as an insulator, preventing the leakage of ions across the axon membrane. This allows for faster conduction of action potentials, as the signal jumps between the unmyelinated regions called nodes of Ranvier.</p> Signup and view all the answers

What is the difference between orthodromic and antidromic propagation of action potentials?

<p>Orthodromic conduction is the normal direction of action potential travel, from the cell body towards the nerve terminals. Antidromic conduction is the reverse direction, from the nerve terminals towards the cell body.</p> Signup and view all the answers

Explain how the concept of 'delayed rectification' relates to potassium channels during an action potential.

<p>Delayed rectification refers to the role of potassium channels in restoring the membrane potential to its resting value after depolarization. They open slowly and allow potassium ions to flow out, counteracting the influx of sodium ions during the rising phase.</p> Signup and view all the answers

What is the role of electrotonic conduction in action potential propagation along myelinated axons?

<p>Electrotonic conduction refers to the passive spread of electrical current along the axon. In myelinated axons, the current flows mainly under the myelin sheath, allowing for rapid conduction without the need for opening of ion channels in those regions.</p> Signup and view all the answers

What is the primary difference between the structure of potassium channels and sodium channels, as described in the text?

<p>Potassium channels are composed of four subunits, while sodium channels are made of four domains. This structural difference contributes to their distinct roles during the action potential.</p> Signup and view all the answers

Why is it important for sodium channels to inactivate during the falling phase of the action potential?

<p>The inactivation of sodium channels prevents the membrane potential from being depolarized further and ensures that the action potential moves in one direction. It also limits the frequency of action potentials that can be generated.</p> Signup and view all the answers

What is the relationship between the concentration of sodium ions inside and outside the cell at rest, and how does this relate to the membrane potential?

<p>At rest, the concentration of sodium ions is higher outside the cell than inside. This concentration gradient, along with the membrane's permeability, helps maintain the negative resting potential of the cell.</p> Signup and view all the answers

Describe the state of the membrane potential during the falling phase of an action potential.

<p>The membrane potential rapidly repolarizes during the falling phase as potassium channels open, allowing potassium ions to flow out of the cell. This counteracts the influx of sodium ions during the rising phase and brings the membrane potential back to its resting value.</p> Signup and view all the answers

What is the primary function of voltage-gated ion channels in the context of the nervous system?

<p>Voltage-gated ion channels serve as molecular switches that control the flow of ions across the cell membrane in response to changes in membrane potential, allowing for the generation and propagation of action potentials.</p> Signup and view all the answers

Explain how the concept of 'threshold' is related to the initiation of an action potential.

<p>The threshold is the minimum level of depolarization required to trigger the opening of a significant number of voltage-gated sodium channels, leading to the rapid depolarization that characterizes the rising phase of an action potential.</p> Signup and view all the answers

How does the action potential relate to the transmission of information within the nervous system?

<p>Action potentials are the primary mechanism for transmitting information along neurons and between neurons. They act like electrical signals that travel along the neuron and can be passed on to other neurons at synapses, allowing for the complex communication that underlies all nervous system functions.</p> Signup and view all the answers

Describe the role of the sodium-potassium pump in maintaining the resting potential of a neuron.

<p>The sodium-potassium pump actively transports sodium ions out of the cell and potassium ions into the cell, maintaining the concentration gradients of these ions that are essential for establishing the resting membrane potential.</p> Signup and view all the answers

What is the main difference between the conduction of action potentials in myelinated and unmyelinated axons?

<p>In myelinated axons, action potentials jump between the nodes of Ranvier, leading to saltatory conduction, which is much faster than the continuous conduction observed in unmyelinated axons.</p> Signup and view all the answers

Describe the typical sodium channel with both activation and inactivation gates. How does it function?

<p>The typical sodium channel consists of two gates: an activation gate and an inactivation gate. When the membrane potential is at rest, the activation gate is closed, preventing sodium ions from passing through. During depolarization, the activation gate opens, allowing sodium ions to flow into the cell. However, after a brief period of time, the inactivation gate closes, blocking further sodium influx. This inactivation prevents the membrane potential from becoming too positive and is vital for the repolarization phase of the action potential.</p> Signup and view all the answers

Explain the significance of the delay in the opening of sodium channels after the voltage is changed to -40 mV. How does this relate to the speed of the action potential?

<p>The delay in sodium channel opening contributes to the duration of the action potential. This delay occurs because it takes time for the activation gate to fully open. The longer the delay, the slower the rate of depolarization and therefore the slower the action potential propagation. Having a short delay ensures faster transmission of the action potential, which is crucial for rapid communication in the nervous system.</p> Signup and view all the answers

Compare and contrast the behavior of sodium (Na+) and potassium (K+) channels in response to changes in membrane potential.

<p>Both sodium and potassium channels respond to changes in membrane potential, but their behaviors differ. Sodium channels open quickly in response to depolarization, allowing a rapid influx of sodium ions. They then quickly inactivate, preventing further sodium entry. Potassium channels, on the other hand, open more slowly in response to depolarization, allowing potassium ions to flow out of the cell, contributing to repolarization. Potassium channels typically remain open until the membrane potential returns to its resting state.</p> Signup and view all the answers

Explain the concept of the 'absolute refractory period' as it relates to sodium channel inactivation.

<p>The absolute refractory period is a time interval during which another action potential cannot be generated, regardless of the strength of the stimulus. This period coincides with the inactivation of sodium channels. Because the sodium channels are inactivated, they cannot respond to depolarization, preventing the generation of another action potential until they re-activate.</p> Signup and view all the answers

How does the measurement of the sodium current during an action potential using patch clamping help us understand the Rising phase of the action potential?

<p>Patch clamping allows us to measure the current flowing through individual ion channels during an action potential. By measuring the sodium current, we observe that it only flows during the Rising phase of the action potential. This demonstrates that the opening of sodium channels, and the subsequent influx of sodium ions, is directly responsible for the rapid depolarization that characterizes the Rising phase.</p> Signup and view all the answers

What is the role of the driving force in the movement of ions through open channels, and how does it relate to the concentration gradient and membrane potential?

<p>The driving force is the combination of electrical and chemical forces that cause ions to move across the membrane. The concentration gradient is the chemical force, pushing ions from a region of high concentration to a region of low concentration. The membrane potential is the electrical force, driving positively charged ions towards a region of negative charge and vice versa. Together, these forces determine the direction and magnitude of ion movement through open channels.</p> Signup and view all the answers

Explain why the non-inactivating potassium channel, activated by depolarization, is important in the context of action potential generation.

<p>The non-inactivating potassium channel contributes to the repolarization phase of the action potential. As the membrane potential rises during depolarization, these channels open slowly and allow potassium ions to flow out of the cell. This efflux of potassium ions helps restore the negative membrane potential, returning the membrane to its resting state. The fact that these channels are non-inactivating ensures that the repolarization process continues until the resting potential is reached.</p> Signup and view all the answers

Briefly describe the significance of Hodgkin and Huxley's research in understanding the action potential, particularly their use of the giant axon of squid.

<p>Hodgkin and Huxley pioneered the understanding of the action potential by using the giant axon of squid, which provided a large and easily accessible system for studying electrical activity in neurons. Their research revealed the fundamental roles of sodium and potassium ions in generating the action potential and the importance of voltage-gated ion channels. Their model, known as the Hodgkin-Huxley cycle, remains a cornerstone of our current understanding of neuronal signaling.</p> Signup and view all the answers

Study Notes

Action Potential

  • Action potentials are the basis of communication in the nervous system.
  • They transfer information over long distances (0.1 mm to 1 m).
  • The fundamental unit is the frequency and discharge pattern. Synonyms include spike, nervous impulse, nervous influx, or discharge.
  • The ionic basis underpins action potentials.
  • The sequence of channel openings and closings produces action potentials.
  • Scientists can study ionic currents and channel function in neurons.
  • The readings for this chapter include Bear, Chapter 4.

Communication in the Nervous System

  • Sensory stimuli activate cutaneous receptors associated with intense deformations.
  • Neural code transmits this information.
  • Action potentials and post-synaptic potentials are part of this code.
  • Interpretation/action results in a response, such as a flexor withdrawal reflex
  • The process continues to other components of the nervous system

Introduction

  • Action potentials transfer information over long distances (0.1 mm to 1 m).
  • This involves a frequency and discharge pattern.
  • Action potentials are often called spikes, nervous impulses, or nervous influxes.

Phases of Action Potentials

  • Includes resting potential, rising phase (depolarization), overshoot, falling phase (repolarization), and hyperpolarization).
  • Additionally includes the refractory periods (Absolute & Relative).

Generation of Action Potentials

  • Action potentials are caused by depolarization exceeding a threshold in the membrane.
  • Stimulation can be electrical, chemical, or mechanical.
  • The "all or nothing" principle dictates how they operate.
  • A chain reaction and feedforward loop are part of this process.
  • Opening of channels permeable to ions like Na+ is involved.

Artificial Injection of Current

  • Scientists create artificial action potentials using microelectrodes and current injection.
  • The process involves stimulating and recording electrodes.
  • Current strength dictates the action potential firing rate.
  • A weaker current does not trigger an action potential.
  • A slightly stronger current initiates a few action potentials.
  • A greater current boosts the discharge frequency

Frequency of Discharge

  • The amplitude of the injected current impacts the discharge frequency.
  • Too weak a stimulation fails to reach the action potential threshold.
  • Just above the threshold, a few action potentials are triggered.
  • Stronger stimulation elevates the discharge frequency.

Mechanism of Generation

  • Describes the fundamental process leading to action potential generation.

Experiment of Hodgkin + Huxley

  • Hodgkin and Huxley researched the giant axon of the squid.
  • They inserted a metal filament into the axon.
  • They assessed the permeability of Na+ and K+.
  • They created a mathematical model explaining the action potential.

Simple Model of an Action Potential

  • At rest, few K+ channels are open.
  • The resting potential is approximately -65 mV.
  • Depolarization triggers rapid Na+ channel opening.
  • This results in a large depolarization.
  • Repolarization occurs due to K+ channel opening and Na+ channel closing.
  • Returning to rest involves K+ and Na+ channels adjusting back to their normal state.

Action Potentials in Reality

  • Action potentials are more complex than initially simplified models.
  • Some channels are inactivated. This means they cannot conduct current regardless of the membrane potential.
  • The inactivation mechanism needs to be studied, including experiments aimed at understanding it.

Cellular Electrophysiology

  • Techniques help observe electrical activity in neurons.
  • These techniques include electrodes and amplifiers, to measure current changes and membrane potentials.
  • Examples of these measurements aim to illustrate which currents cross the membrane during an action potential.

Electrophysiology

  • Laboratory techniques enable the measurement of electrical signals in the nervous system.
  • The relationship between voltage (Vm), resistance (Rm), and current (Im) in a neuron can be measured.
  • It is often impossible to measure both membrane potential and current at the same time.

Imposed Voltage vs Imposed Current

  • Current clamping monitors the membrane voltage.
  • Voltage clamping monitors the current through ion channels.
  • Each technique helps observe different characteristics of the neuron.

Current-Clamp

  • Used to measure the voltage response in a neuron to injected current.

Voltage-Clamp

  • Methods allow controlled measurement of membrane current (Im) while maintaining a set membrane potential (Vm using feedback circuits.
  • Used to measure ionic currents during specific membrane potential conditions.

Voltage Clamp Methods

  • Injecting a current and measuring the resultant voltage is part of this technique.
  • Adjusting the current to maintain the target voltage (Vclamp) is involved.

Voltage Clamp Measurements

  • Voltage clamping measures currents associated with Na+ and K+ channels opening and closing.
  • The technique helps detail voltage-dependent inactivation.

Can We Determine the Inactivation Mechanism?

  • Analyses of action potentials examine Na+ current inactivation.
  • Research into the reasons for inactivation is part of this study.
  • The underlying mechanisms of this process are important.

Patch-Clamping

  • A technique used to observe the activity of single ion channels.
  • It manipulates membrane potentials and records the current going through ion channels.
  • Membrane portions are held in a pipet for observation.

Leak Channels vs Voltage-Gated Channels

  • Leak channels operate consistently independent of membrane potential.
  • Voltage-gated channels operate in response to changes in membrane potential.

When the Activation Gate of a Channel Opens

  • The "activation" gate of the channel controls transitions between open and closed states due to changes in membrane potential.
  • The process is reversible.
  • An "inactivation" gate, in some channels, further affects the functionality of the channel opening and closing.

Some V-Gated Channels

  • Such channels have both gates, which need to be open for current flow.

One Gate in a Closed Position

  • Having one gate in the closed state is enough to prevent current flow.

Voltage Can Drive Channel Conformation

  • Membrane potential changes and regulates channel conformations, impacting ion current.
  • The conformations involve stages of activation, inactivation, closing, and recovery.

An inactivating Na+ Channel

  • Observation of Na+ channel activity shows they inactivate (close) after some time at -40 mV.

Recording of Na+ Channels

  • Na+ channels open very fast, but stay open for a short period (approximately 1 ms).
  • Closing of the Na+ channels via inactivation is another critical component of action potentials.
  • Mechanisms such as "ball and chain" are part of the understanding of this inactivation.

Phases of Action Potentials

  • Patch-clamping aids in measuring Na+ currents during action potentials.
  • This details the specific currents entering the cell. Na+ current only enters during the rising phase.

A Non-inactivating K+ Channel

  • Non-inactivating K+ channels are activated by depolarization, and their activity differs substantially from that of Na+ channels.

Phases of Action Potentials (K+)

  • Measuring K+ currents in individual channels during action potential is possible.
  • The K+ current enters at the end of the rising phase, peaking at the onset of the falling phase.

K+ Channels vs Na+ Channels

  • Both K+ and Na+ channels respond differently to voltage change and membrane potential. Their structure and inactivation characteristics are distinct.

Generation of Action Potential

  • This discussion covers the phases of action potential generation—from rest to different phases with the respective ion currents (Na+ & K+)

Propagation of Action Potentials

  • Action potentials travel in one direction (orthodromic) towards the nerve terminals or in the opposite direction (antidromic) toward the cell body.
  • The duration of action potential is 2 ms.
  • Typical nerve conduction velocity is approximately 10 m/s.

Factors Influencing Conduction Velocity: Saltatory Conduction

  • The myelin sheath is crucial for faster action potential propagation.
  • Schwann cells and oligodendrocytes form the myelin.
  • Uninsulated areas called Nodes of Ranvier enable rapid ion movement.
  • Electrotonic and active conduction occur under myelin and at Nodes of Ranvier, respectively

Action Potentials, Axons, and Dendrites

  • Sensory neurons' action potential initiation sites differ from others.
  • Nerve terminals (dendritic extremities) are also important sites.
  • These sites are often critical to neuronal function.

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This quiz explores key concepts from Hodgkin and Huxley's research on action potentials, including the roles of sodium and potassium ions, the significance of the squid giant axon, and the mechanisms of depolarization and repolarization. Dive into the details of membrane potential and the importance of ion channel dynamics in neuronal signaling.

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