Learning objectives
By the end of this section, you will be able to:
Describe how the movement of ions across the neuron membrane leads to an action potential.
- Describe the membrane components that establish the resting membrane potential.
- Describe the changes that occur in the membrane that result in the action potential.
The functions of the nervous system (sensation, integration, and response) depend on the functions of the neurons underlying these pathways. To understand how neurons can communicate, it is necessary to describe the role of amembrana excitablein generating these signals. The basis of this process is theaction potential.An action potential is a predictable change in membrane potential that occurs due to the opening and closing of voltage-gated ion channels in the cell membrane.
Most cells in the body use charged particles (ions) to create electrochemical charge across the cell membrane. In an earlier chapter, we described how muscle cells contract as a function of the movement of ions across the cell membrane. In order for skeletal muscles to contract, due to excitation-contraction coupling, they require input from a neuron. Both muscle and nerve cells use a specialized signal-conducting cell membrane to regulate ionic movement between the extracellular fluid and the cytosol.
As you learned in the chapter on cells, the cell membrane is primarily responsible for regulating what can pass through the membrane. The cell membrane is a phospholipid bilayer, so only substances that can pass directly through the hydrophobic core can diffuse unaided. Charged particles, which are hydrophilic, cannot cross the cell membrane without help (Figure 12.5.1🇧🇷 Specific transmembrane channel proteins allow charged ions to move across the membrane. Several passive transport channels as well as active transport pumps are required to generate a transmembrane potential and an action potential. Of special interest is the transporter protein known assodium/potassium pumpwhich uses energy to move sodium ions (Na+) of a cell and potassium ions (K+) in a cell, thus regulating the concentration of ions on either side of the cell membrane.
The sodium/potassium pump requires energy in the form of adenosine triphosphate (ATP), which is why it is also called the ATPase pump. As explained in the cells chapter, the concentration of Na+is higher outside the cell than inside, and the concentration of K+it is larger inside the cell than outside. So this pump is working against the concentration gradients of sodium and potassium ions, so it requires energy. then a+/K+The ATPase pump maintains these important ion concentration gradients.
Ion channels are pores that allow specific charged particles to pass through the membrane in response to an existing electrochemical gradient. Proteins can cross the cell membrane, including its hydrophobic core, and can interact with charged ions due to the different properties of amino acids found in specific regions of the protein channel. Hydrophobic amino acids are found in regions adjacent to the hydrocarbon tails of phospholipids, where hydrophilic amino acids are exposed to the fluid environments of extracellular fluid and cytosol. Furthermore, the ions will interact with hydrophilic amino acids, which will be selective for the charge of the ion. Channels for cations (positive ions) will have negatively charged side chains in the pore. Channels for anions (negative ions) will have positively charged side chains in the pore. The channel pore diameter also affects the specific ions that can pass through. Some ion channels are charge selective but not necessarily size selective. These non-specific channels allow cations, particularly Na+,K+, and approx.2+— cross the membrane but exclude anions.
Some ion channels do not allow ions to diffuse freely across the membrane, but arecerradoinstead of. Abinder controlled channelit opens because a molecule, or ligand, binds to the extracellular region of the channel (Figure 12.5.2).
Amechanically closed channelit opens due to a physical distortion of the cell membrane. Many channels associated with the sense of touch are mechanically controlled. For example, when pressure is applied to the skin, mechanically closed channels in the subcutaneous receptors open and allow the entry of ions (Figure 12.5.3).
Avoltage dependent channelIt is a channel that responds to changes in the electrical properties of the membrane in which it is inserted. Normally, the inner part of the membrane has a negative voltage. When this voltage becomes less negative and reaches a specific value for the channel, it opens, allowing ions to cross the membrane (Figure 12.5.4).
Aleak channelit closes randomly, which means it opens and closes randomly, hence the reference to fugue. There is no actual event that opens the channel; instead, it has an intrinsic rate of change between open and closed states. Leakage channels contribute to the resting transmembrane tension of the excitable membrane.Figure 12.5.5).
oMembrane potentialis a charge distribution across the cell membrane, measured in millivolts (mV). The standard is to compare the inside of the cell to the outside, so the membrane potential is a value that represents the charge on the intracellular side of the membrane (based on the outside being zero, in relative terms;Figure 12.5.6).
Normally, there is an overall net neutral charge between the extracellular and intracellular environments of the neuron. However, a small charge difference occurs right at the surface of the membrane, both internally and externally. It is the difference in this very limited region that has the power to generate electrical signals, including action potentials, in neurons and muscle cells.
When the cell is at rest, ions are distributed across the membrane in a very predictable way. Na concentration+outside the cell is 10 times greater than the concentration inside. Also, the concentration of K+inside the cell is greater than outside. The cytosol contains a high concentration of anions, in the form of phosphate ions and negatively charged proteins. With ions distributed across the membrane at these concentrations, the charge difference is described as theresting membrane potential🇧🇷 The exact value measured for the resting membrane potential varies between cells, but -70 mV is a commonly reported value. This voltage would actually be much lower except for the contributions of some important proteins in the membrane. Leakage channels allow Na+move slowly towards cell or K+move slowly out, and the Na+/K+pump restores their concentration gradients across the membrane. This may seem like a waste of energy, but each has a role in maintaining membrane potential.
action potential
The resting membrane potential describes the steady state of the cell, which is a dynamic equilibrium process in which ions filter down their concentration gradient and ions are pumped back down their concentration gradient. Without any external influence, the resting membrane potential will be maintained. To initiate an electrical signal, the membrane potential must become more positive.
This begins with the opening of voltage-gated Na+ channels in the neuron's membrane. As the concentration of Na+is greater outside the cell than inside the cell by a factor of 10, ions will enter the cell, driven by chemical and electrical gradients. Since sodium is a positively charged ion, entering the cell will immediately change the relative voltage within the cell membrane. The resting membrane potential is about -70 mV, so sodium cation entering the cell will cause the membrane to become less negative. This is known asdepolarization, which means that the membrane potential approaches zero (becomes less polarized). The Na concentration gradient+it is so strong that it will continue to enter the cell even after the membrane potential has become zero, so the voltage immediately around the pore begins to be positive.
As the membrane potential reaches +30 mV, voltage-gated potassium channels open in the membrane that take longer to open. An electrochemical gradient acts on K+, what's more. To ask+begins to leave the cell, taking a positive charge with it, the membrane potential begins to fall back toward its resting voltage. is namedrepolarization, which means that the membrane voltage returns to the value of -70 mV of the resting membrane potential.
Repolarization returns the membrane potential to -70 mV of the resting potential, but rises above that value. Potassium ions reach equilibrium when the membrane voltage is below -70 mV, then a period of hyperpolarization occurs while K+the channels are open. those k+the channels are slightly late in closing, which explains this brief excess.
What has been described here is the action potential, which is displayed as a graph of voltage over time inFigure 12.5.7🇧🇷 It is the electrical signal that generates the nervous tissue for communication. The change in membrane voltage from -70 mV at rest to +30 mV at the end of depolarization is a 100 mV change.
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What happens across the membrane of an electrically active cell is a dynamic process that is difficult to visualize with still images or text descriptions. watch thisanimationto learn more about this process. What is the difference between the driving force of Na+mi k+🇧🇷 And how is the movement of these two ions similar?
The membrane potential will remain at the resting voltage until something changes. To initiate an action potential, the membrane potential must change from the resting potential of approximately -70 mV to the threshold voltage of -55 mV. Once the cell reaches threshold, voltage-gated sodium channels open, and the predictable membrane potential changes as an action potential. Any subthreshold depolarization that does not change the membrane potential to -55 mV or more will not reach threshold and therefore will not result in an action potential. Furthermore, any stimulus that depolarizes the membrane to -55 mV or more will cause a large number of channels to open and initiate an action potential.
Because of the predictable changes that occur when the threshold is reached, the action potential is called "all or nothing." This means that either the action potential occurs and is repeated along the entire length of the neuron, or no action potential occurs at all. A stronger stimulus, which can depolarize the membrane well beyond threshold, will not produce a "major" action potential. Either the membrane reaches threshold and everything happens as described above, or the membrane does not reach threshold and nothing else happens. All action potentials peak at the same voltage (+30 mV), so one action potential is not higher than the other. Stronger stimuli will initiate multiple action potentials more quickly, but individual signals are not larger.
As we have seen, the depolarization and repolarization of an action potential depends on two types of channels (the Na+channel and the dependent voltage K+channel). The voltage dependent Na+the channel actually has two gates. one is theactivation gate, which opens when the membrane potential crosses -55 mV. the other door isinactivation gate, which closes after a specified period of time, on the order of a fraction of a millisecond. When a cell is at rest, the activation gate is closed and the inactivation gate is open. However, when the threshold is reached, the activation gate opens, allowing Na+run to the cell Synchronized with the depolarization peak, the inactivation gate closes. During repolarization, sodium cannot enter the cell. When the membrane potential again exceeds -55 mV, the activation gate closes. After that, the inactivation gate reopens, leaving the channel ready to start the whole process over again.
The dependent voltage K+The channel has only one gate, which is sensitive to a membrane voltage of -50 mV. However, it does not open as quickly as voltage-dependent Na.+the channel does. It takes a fraction of a millisecond for the K+ channel to open once the voltage is reached, which coincides exactly with the moment when Na+Flow peaks. So K voltage dependent+channels open exactly when the voltage-gated Na+channels are being disabled. As the membrane potential repolarizes and the voltage drops back below -50 mV, the K+ channels begin to close. Potassium continues to leave the cell for a short time and the membrane potential becomes more negative, resulting in excessive hyperpolarization. The K+ channels then close and the membrane returns to the resting potential due to the continued activity of the leaky and Na channels.+/K+ATPase pump.
This all happens in about 2 milliseconds (Figure 12.5.8🇧🇷 While one action potential is in progress, another cannot be initiated. This effect is calledrefractory period🇧🇷 There are two phases of the refractory period: theabsolute refractory periodIt's inrelative refractory period🇧🇷 During the absolute refractory period, no other action potential will be initiated. This is due to the voltage-dependent gate of Na inactivation.+channel. Once the Na+ channel has returned to its resting conformation, a new action potential could be initiated during the hyperpolarization phase, but only by a stronger stimulus than the one that initiated the current action potential.
Action potential propagation
The action potential is initiated at the beginning of the axon, in what is called the initial segment (activation zone)🇧🇷 Here a rapid depolarization can occur due to a high voltage dependent Na density.+channels. Along the axon, the action potential spreads because more Na+channels open as depolarization spreads. This scattering occurs because Na+it enters the channel and moves along the inside of the cell membrane. like nothing+moves, or flows, a short distance along the cell membrane, its positive charge depolarizes the cell membrane a little more. As depolarization spreads, new Na+the channels open and more ions enter the cell, extending the depolarization a bit more.
As voltage dependent Na+channels are inactivated at the peak of depolarization, they cannot be reopened for a short time (absolute refractory period). Because of this, positive ions returning to previously open channels have no effect. The action potential must propagate from the trigger zone to the axon terminals.
Spreading, as described above, is applied to unmyelinated axons. When there is myelination, the action potential propagates differently and is optimized for the speed of signal conduction. Sodium ions entering the cell at the trigger zone begin to propagate along the axonal segment, but there is no voltage-gated Na.+channels to the first Ranvier node. Since there is no constant opening of these channels along the axonal segment, depolarization propagates at an optimal rate. The distance between nodes is the ideal distance to keep the membrane still depolarized above threshold at the next node. And in+extends along the inside of the membrane of the axonal segment, the charge begins to dissipate. If the node had been further down the axon, this depolarization would have fallen too low for voltage-gated Na.+channels that will be activated in the next Ranvier node. If the nodes were closer together, the rate of propagation would be slower.
Propagation along an unmyelinated axon is calledcontinuous driving🇧🇷 along the length of a myelinated axon is calledsaltatory driving🇧🇷 Continuous driving is slow because there is always Na+channels opening, and more and more Na+he is running towards the cell. Saltatory conduction is faster because the action potential “jumps” from one node to the next (saltare = “jump”), and the new entry of Na+renews the depolarized membrane. Along with axon myelination, axon diameter can influence conduction velocity. Just as water flows faster in a wide river than in a narrow stream, Na+Axon-based depolarization spreads faster down a wide axon than down a narrow axon. This concept is known asenduranceand in general it is true for electrical wires or pipes as it is for axons, although the specific conditions are different on the scales of electrons or ions versus water in a river.
Homeostatic imbalances -potassium concentration
Glial cells, especially astrocytes, are responsible for maintaining the chemical environment of the CNS tissue. Ion concentrations in the extracellular fluid underlie how membrane potential is established and changes in electrochemical signaling. If the ionic balance is disturbed, drastic results are possible.
Usually the concentration of K+is greater inside the neuron than outside. After the repolarization phase of the action potential, K+leak channels and Na+/K+The pumps ensure that the ions return to their original locations. After a stroke or other ischemic event, extracellular K+levels are high. Astrocytes in the area are equipped to remove excess K+to help the bomb. But when the level is too unbalanced, the effects can be irreversible.
Astrocytes can become reactive in cases like these, affecting their ability to maintain the local chemical environment. Glial cells enlarge and their processes swell. they lose their K+the damping capacity and the operation of the pump are affected or even reversed. One of the first signs of cell disease is this "leakage" of sodium ions into the cells of the body. This sodium/potassium imbalance negatively affects the internal chemistry of cells, preventing them from functioning normally.
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visit thislocalSee a virtual neurophysiology lab and observe electrophysiological processes in the nervous system, where scientists directly measure electrical signals produced by neurons. Often action potentials happen so fast that looking at a screen to see them isn't helpful. A loudspeaker works with the recorded signals from a neuron and makes a "click" each time the neuron fires an action potential. These action potentials fire so fast that they sound like static on the radio. Electrophysiologists can recognize the patterns within this static to understand what is happening. Why is the leech model used to measure the electrical activity of neurons instead of using humans?
Chapter Review
The nervous system is characterized by electrical signals that are sent from one area to another. Whether these areas are near or far, the signal must travel the length of an axon. The basis of the electrical signal is the controlled distribution of ions across the membrane. Transmembrane ion channels regulate when ions can enter or leave the cell to generate a precise signal. This signal is the action potential that has a very characteristic shape based on the changes in voltage across the membrane over a given period of time.
The membrane is normally at rest with Na+mi k+concentration on both sides. A stimulus will initiate depolarization of the membrane, and voltage-gated channels will result in further depolarization followed by repolarization of the membrane. A slight excess of hyperpolarization marks the end of the action potential. While an action potential is in progress, another cannot be generated under the same conditions. While the voltage dependent Na+the channel is inactive, absolutely no action potentials can be generated. Once this channel has returned to its resting state, a new action potential is possible, but it must be initiated by a relatively stronger stimulus to overcome the hyperpolarized state.
The action potential travels down the axon as voltage-gated ion channels open by scattered depolarization. In unmyelinated axons, this happens continuously because there are voltage-gated channels throughout the membrane. In myelinated axons, propagation is described as saltatory because voltage-gated channels are only found in the nodes of Ranvier, and electrical events appear to "jump" from node to node. Saltatory conduction is faster than continuous conduction, which means that myelinated axons propagate their signals faster. The diameter of the axon also makes a difference, since ions that diffuse into the cell have less resistance over a larger space.
Interactive Link Questions
What happens across the membrane of an electrically active cell is a dynamic process that is difficult to visualize with still images or text descriptions. watch thisanimationto really understand the process. What is the difference between the driving force of Na+mi k+🇧🇷 And how is the movement of these two ions similar?
Sodium enters the cell due to the huge concentration gradient, while potassium leaves due to depolarization caused by sodium. However, both move in their respective gradients, towards equilibrium.
visit thislocalSee a virtual neurophysiology lab and observe electrophysiological processes in the nervous system, where scientists directly measure electrical signals produced by neurons. Often action potentials happen so fast that looking at a screen to see them isn't helpful. A loudspeaker works with the recorded signals from a neuron and makes a "click" each time the neuron fires an action potential. These action potentials fire so fast that they sound like static on the radio. Electrophysiologists can recognize the patterns within this static to understand what is happening. Why is the leech model used to measure the electrical activity of neurons instead of using humans?
Electrophysiology properties are common to all animals, so using the leech is an easier approach to study the properties of these cells. There are differences between the nervous systems of invertebrates (such as a leech) and vertebrates, but not for what these experiments study.
review questions
critical thinking questions
1. What does it mean for an action potential to be an “all or nothing” event?
2. Often the conscious perception of pain is delayed due to the time it takes for sensations to reach the cerebral cortex. Why would this be the case based on potential axon spread?
Glossary
- absolute refractory period
- time during an action period when another action potential cannot be generated because Na+the channel is inactive
- activation gate
- voltage dependent part of Na+channel that opens when the membrane voltage reaches threshold
- continuous driving
- slow propagation of an action potential along an unmyelinated axon due to voltage-gated Na+channels located along the entire length of the cell membrane
- depolarization
- change in cell membrane potential from rest to zero
- electrochemical exclusion
- principle of selectively allowing ions through a channel based on their charge
- membrana excitable
- cell membrane that regulates the movement of ions so that an electrical signal can be generated
- cerrado
- property of a channel that determines how it opens under specific conditions, such as changes in stress or physical strain
- inactivation gate
- part of a voltage dependent Na+channel that closes when the membrane potential reaches +30 mV
- ionotropic receptor
- neurotransmitter receptor that acts as an ion channel gate and is opened by neurotransmitter binding
- leak channel
- ion channel that opens randomly and is not controlled by a specific event, also known as an uncontrolled channel
- ligand-gated channels
- another name for an ionotropic receptor for which a neurotransmitter is the ligand
- mechanically closed channel
- ion channel that opens when a physical event directly affects the structure of the protein
- Membrane potential
- charge distribution across the cell membrane, based on ion charges
- non-specific channel
- channel that is nonspecific for one ion over another, such as a nonspecific cation channel that allows any positively charged ion to cross the membrane
- refractory period
- time after initiation of an action potential when another action potential cannot be generated
- relative refractory period
- time during the refractory period when a new action potential can only be initiated by a stimulus stronger than the current action potential because voltage-dependent K+the channels are not closed
- repolarization
- return of the membrane potential to its normally negative voltage at the end of the action potential
- endurance
- property of an axon that relates to the ability of particles to diffuse through the cytoplasm; this is inversely proportional to the fiber diameter
- resting membrane potential
- the voltage difference measured across a cell membrane under steady-state conditions, typically -70 mV
- saltatory driving
- rapid propagation of the action potential along a myelinated axon due to voltage-gated Na+channels are present only in Ranvier nodes
- size exclusion
- principle of selectively allowing ions through a channel based on their relative size
- voltage dependent channel
- ion channel that opens due to a change in charge distributed across the membrane where it is located
Solutions
Answers to critical thinking questions.
- The cell membrane must reach threshold before voltage-dependent Na+open channels. If the threshold is not reached, these channels do not open, and the depolarization phase of the action potential does not occur, the cell membrane will simply return to its resting state.
- The axons of pain-sensitive sensory neurons are thin and unmyelinated, so pain sensation takes longer to reach the brain than other sensations.