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Biology 230 - Molecules and Cells

Membrane Potential, Ion Transport and Nerve Impulse

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  • acetylcholine
  • acetylcholine receptor
  • acetylcholinesterase
  • action potential
  • axon
  • cell body
  • dendrite
  • depolarization
  • electrical excitability
  • equilibrium potential (E)
  • gamma-aminobutyric acid (GABA)
  • hyperpolarization
  • ligand-gated ion channel
  • myelin sheath
  • neuron
  • neurotransmitter
  • neurotransmitter receptor
  • Nernst equation
  • nerve impulse
  • nodes of Ranvier
  • presynaptic cell
  • postsynaptic cell
  • potassium leak channels
  • repolarization
  • reuptake
  • synapse
  • synaptic cleft
  • synaptic transmission
  • synaptic vesicles
  • support cells
  • terminal bulb
  • voltage-gated ion channel
  • voltage sensor

Introduction and Goals

This tutorial will examine how ion transport is used to send signals in the animal nervous system. Neurons, a specialized type of cell of the nervous system, receive and send signals to regulate all conscious and unconscious movement, thought and behavior. Neurons generate and transmit electrochemical signals. The role of ion channels in producing and conducting these electrochemical signals will be described. In addition, you will learn how a nerve impulse is propagated along the membrane of one cell, and how it is converted to a chemical signal and sent to an adjacent target cell.

By the end of this tutorial you should know:

  • The unique structure of a neuron
  • The definition of a resting potential, and how it is maintained
  • The mechanism of voltage-gated ion channels
  • The definition of an action potential, and how it is achieved
  • How an action potential is propagated along an axon
  • How an action potential triggers the release of a chemical signal
  • How a chemical signal is received, and how it induces a change in the membrane potential of a target cell

The Neuron

Figure 1.  A typical neuron. The cell body, containing the nucleus, is the metabolic center of the cell. The dendrites receive electrochemical signals from other neurons. The axon transmits the nerve impulse away from the cell body toward the terminal bulb, which makes contact with a target cell.

The animal nervous system is composed of two cell types: neurons and support cells. Neurons produce and conduct electrochemical signals, while support cellsaid the neurons in a variety of ways. Neurons are distinguished by their ability to respond to external stimuli by altering their membrane potential. This property is referred to as electrical excitability. There are many types of neurons, with distinct shapes and functions, however they all share some common features (illustrated in Figure 1). A neuron is composed of a cell body, dendrites, and an axon. The cell body is the metabolic center of the cell, containing the nucleus. The dendrites are thin, branched projections that receive electrochemical signals, usually from other neurons. An axonis a long process that transmits a signal away from the cell body toward the adjacent cell, either another neuron, a muscle, or a gland. The length of an axon can vary from a millimeter to a over a meter. The distal end of an axon that will make contact with a target cell is termed the terminal bulb. A nerve impulse represents the propagation of a change in membrane potential through the cell body and along the axon. The transmission of a nerve impulse occurs very rapidly, in a few milliseconds. Although the impulse may be conducted along many neurons, there is no significant decay in the amplitude of the signal.

Neurons are triggered by stimuli, chemical and electrical, and these signals are transmitted along the length of the axon by briefly altering the membrane potential. Remember from the previous tutorial, a membrane potential is the difference in charge across a membrane due to the gradient of ions across that membrane. The resting membrane potential (often referred to as resting potential) for a typical neuron is -70 mV. This indicates that the inside of the cell is negatively charged compared to the outside of the cell. The ionic concentrations of the most common ions inside and outside of a mammalian motor neuron are shown in Table 1.


Concentration inside

Concentration outside


10 mM

145 mM


140 mM

5 mM


10 mM

125 mM

Resting Membrane Potential (continued)

Figure 2.  Measuring membrane potential. The membrane potential (the difference in charge across a membrane) of a neuron is measured with a voltmeter. The recording electrode is placed inside the axon and the reference electrode is placed just outside of the axon in the extracellular fluid. The membrane potential is the difference in charge between these two electrodes. At resting, most neurons have a negative membrane potential; therefore, they have a negative charge on the intracellular side of the axon membrane, compared to the positive charge of the extracellular fluid across the membrane.

The resting membrane potential of a neuron can be measured directly with a voltmeter. It is the difference in voltage between two electrodes; the recording electrode is placed inside the axon (on the intracellular side of the plasma membrane), and the reference electrode is placed just outside of the axon (see Figure 2).

A negative membrane potential arises because of the permeability of the plasma membrane to different molecules. Large, negatively charged organic molecules are trapped inside the cell, whereas positively charged ions can move across the membrane. Small, positively charged ions (e.g. sodium and potassium) are pumped across the membrane by the Na^,K^-ATPase in a reciprocal fashion, resulting in steep gradients of sodium ions outside the cell and potassium ions inside the cell. A typical resting neuron is also permeable to potassium ions via open potassium ion channels (termed potassium leak channels). Potassium ions flow out of the cell and contribute to the accumulation of the negative charge in the interior of the cell, compared to the exterior. The diffusion of potassium ions via the leak channels is regulated by two opposing forces: the concentration gradient, which favors an outflow of potassium ions; and the voltage gradient, which favors an influx of potassium ions. When these two forces balance each other, equilibrium is achieved. The membrane potential at which this equilibrium is reached for any given ion is called the equilibrium potential (E), and it is calculated from the Nernst equation:

Ex is the equilibrium potential for any given ion (X), R is the gas constant (1.987 cal/molK), T is the temperature in K, [X]out/[X]inis the ratio of the ion concentration outside the cell over the ion concentration inside the cell, z is the charge of the ion, and F is the Farady constant (23,062 cal/V-mol). The Nernst equation calculates the equilibrium potential for an ion, assuming the membrane is only permeable to that particular ion. For potassium ions the Nernst equation is written:

and E[K+] is -91mV, which is close to the resting potential of a typical neuron (-70mV); therefore, it is the flow of potassium ions through the leak channels that is considered the most important factor in determining the resting potential of a cell. However, the actual membrane potential is different from the potassium ion equilibrium potential because the membrane is also slightly permeable to other ions.

Voltage-Gated Ion Channels

Figure 3. The mechanism of a voltage-gated ion channel. At resting, the voltage-gated ion channel is closed and ions cannot pass. In response to neuron stimulation, the membrane potential will increase, which results in the opening of the voltage-gated ion channel. The initial change in membrane potential is detected by the voltage sensor, which induces a conformational change in the channel and allows ions to pass. The channel remains open briefly, and then undergoes a further conformational change in which it is inactivated by the so-called "ball and chain" portion of the protein (shown in black and green). The channel will remain inactive and refractory to changes in membrane potential for a brief period of time before returning to the active, but closed, resting position.

Neuron stimulation can be regulated in the laboratory by inserting an electrode into an axon and delivering a pulse of electric current. Historically, the giant axons of squid, which are 1 mm in diameter, were used to observe the local changes in membrane potential. A characteristic increase and then decrease in membrane potential is observed, which can be correlated with the movement of sodium and potassium ions across the membrane. 

In response to neuron stimulation, voltage-gated ion channels are opened, allowing the rapid and brief flow of sodium ions and potassium ions across the plasma membrane. Voltage-gated ion channels are similar to ordinary ion channels (reviewed in the previous tutorial - Passive and Active Transport), but with one important difference; they are only open in response to a voltage change across the membrane. See Figure 3for an illustration. In a resting neuron, the voltage-gated ion channels are in the closed conformation and ions cannot pass through. In response to neuron stimulation, the voltage-gated ion channels open. The best-studied channels are the voltage-gated potassium channels, for which there are X-ray crystallographic data, although the mechanism of action is likely to be similar for other voltage-gated ion channels. These channels contain a region of protein termed the voltage sensor, which is comprised of several positively charged amino acid residues that sense the change in voltage across the membrane. In the resting state, the ion channel is closed or gated; however, a change in membrane potential results in a conformational change of the ion channel, which opens it up to allow diffusion of the ion. Generally, voltage-gated ion channels are only open for a fraction of a second, when they either undergo a conformational change to the closed configuration or they are inactivated and become refractory (resistant) to changes in membrane potential for a brief period of time.

The action potential

(stages of an action potential)

An action potentialis a distinct change in membrane potential that occurs in response to a stimulation (illustrated in the animation). An action potential can be classified into four distinct phases that correlate with changes in sodium ion and potassium ion permeability. The four phases of an action potential are resting, depolarization, repolarization, and hyperpolarization. The resting neuron has a membrane potential of -70 mV, which is maintained by the potassium leak channels. The action potential is initiated by depolarization, a reduction in the difference in charge across the membrane. The stimulation of the neuron must depolarize the membrane beyond the threshold level (-50 mV). If the initial depolarization does not exceed the threshold level, then the action potential will not proceed and the membrane potential will return to the resting potential. If the threshold is exceeded, then the voltage-gated sodium channels are opened and there is a rapid inflow of sodium ions, reversing the membrane potential from a negative value to a positive value. Depolarization typically occurs in less than one millisecond, then the voltage-gated sodium channels are inactivated. Depolarization triggers the voltage-gated potassium channels to open, and the third phase of the action potential (i.e. repolarization) is initiated. During repolarization, the voltage-gated potassium channels open and there is an efflux of potassium ions that restores the negative charge to the interior of the cell. The voltage-gated potassium channels are slow to close after the change in membrane potential, and as a result hyperpolarization (increasing the membrane potential beyond the level of the resting potential) occurs. The potassium leak channels then reestablish the resting membrane potential. During this period, the sodium channels are restored to the active, but closed, state and this portion of the axon is ready to repeat the action potential in response to further stimulation.

Propagation of the Action Potential

Figure 4.  Propagation of an action potential along an axon. An action potential is propagated in one direction, away from the cell body and toward the terminal bulb. This illustration shows four distinct domains of the axon membrane and the conformational states of the voltage-gated sodium channels in each domain, with the action potential being propagated from left to right. The region of the membrane that is depolarized contains open voltage-gated sodium channels that allow the influx of sodium ions. This results in an increase in the membrane potential ???? . This depolarization will trigger a new action potential in the region of membrane immediately in front of it (region where next action potential will be triggered) by the opening of the voltage-gated sodium channels. Immediately behind the depolarized region of the membrane is the region that is refractory, which cannot initiate a new action potential. The action potential has already occurred in this region and the voltage-gated sodium channels remain inactive; therefore, they are resistant to the membrane depolarization in the adjacent region and do not open. Further back, along the axon, is the region at resting state, which has undergone an action potential and recovered from the refractory period and is now ready for the next action potential.

The action potential occurs over a relatively small area of the axon membrane. It spreads along the full length of the axon through waves of depolarization and repolarization that travel along to the terminal bulb. In most invertebrates the entire length of the axon is capable of an action potential, and the initial depolarization of one small patch of the axon triggers a new action potential in the adjacent area of the axon. To say that the action potential spreads along the axon is somewhat misleading. In fact, it is regenerated anew in each new patch of membrane extending toward the terminus. In this way, the amplitude of the action potential is not diminished as it moves along the length of the axon. The action potential spreads because the region that has just produced an action potential is refractory for a brief period of time, but the adjacent region slightly depolarizes, triggering a new action potential (see Figure 4).  

Figure  5.  A myelinated axon. Most vertebrate neurons possess a myelin sheath wrapped around the axon. The myelin sheath is composed of the plasma membranes of support cells. In this example of a motor neuron, the axon is encircled by Schwann cells. The myelin sheath is periodically interrupted at the nodes of Ranvier. An action potential can only occur at the nodes of Ranvier. Depolarization at one node triggers an action potential in the adjacent node. The action potentials are propagated toward the terminal bulb.

Most vertebrate axons are covered by lipid-rich myelin sheaths, produced by support cells that act to insulate the axon and restrict the region of the axon that can produce an action potential. The myelin sheath is not continuous but has interruptions referred to as the nodes of Ranvier. Voltage-gated ion channels are clustered at these nodes, where action potentials can be renewed. In a myelinated axon, the action potential does not propagate continuously along the axon (as described above). Rather, depolarization occurs only at the nodes and the action potential at one node triggers depolarization at the next node (see Figure 5). In this fashion, the action potential is propagated along greater distances, increasing the conductance by twenty-fold.  

The Synapse

A neuron is linked to its target cell, which can be either another neuron, muscle or gland, through a specialized junction called a synapse. A synapse is the point of contact between the terminus of the axon and its target cell. Usually there is no direct contact between the two cells, but rather, a small gap termed the synaptic cleft. The neuron conducting the nerve impulse along its axon is referred to as the presynaptic cell, and the receiving cell on the other side of the synaptic cleft is referred to as the postsynaptic cell. How does the propagating action potential in the presynaptic cell get transmitted to the postsynaptic cell? Synaptic transmissionis the signaling that occurs between cells across the synaptic cleft. In most synapses this is mediated by the release of chemical signals from the presynaptic cell that crosses the synaptic cleft, which triggers a change in the postsynaptic cell. These chemical signals, termed neurotransmitters, are a diverse collection of molecules, including small peptides, amino acids and their derivatives, and other small organic molecules.

Chemical transmission at the synapse

Figure 6. Chemical transmission at the synapse.The action potential in the presynaptic cell is transmitted to the postsynaptic cell via a chemical signal, which, in turn, triggers an action potential in the postsynaptic cell. When the action potential of the presynaptic cell reaches the terminal bulb, it triggers the opening of voltage-gated calcium channels in the plasma membrane. Calcium ions flow into the presynaptic cell. The elevated intracellular concentration of calcium triggers the fusion of synaptic vesicles with the plasma membrane of the terminal bulb. The synaptic vesicles reside in the terminal bulb, filled with neurotransmitters. When they fuse with the plasma membrane, the neurotransmitters are released into the synaptic cleft. Extracellular neurotransmitters bind to specific receptors in the plasma membrane of the postsynaptic cell. Upon the binding of neurotransmitter to its receptor, an action potential is triggered in the postsynaptic cell.

The action potential of the presynaptic cell triggers the release of neurotransmitters into the synaptic cleft via regulated exocytosis. Once in the synaptic cleft, the neurotransmitters bind to distinct receptors on the surface of the postsynaptic cell and initiate a change in membrane potential. The mechanism of synaptic transmission is described below and is illustrated in Figure 6. Neurotransmitters are generally stored in synaptic vesicles(a specialized type of secretory vesicle) located in the terminal bulb of the axon of the presynaptic cell. As the nerve impulse is propagated along the length of the axon, it triggers the opening of voltage-gated calcium channels that are clustered at the plasma membrane of the terminal bulb of the presynaptic cell. When these channels are open there is a large influx of calcium ions into the cell. The increase in intracellular calcium results in the rapid fusion of the synaptic vesicles with the plasma membrane and the release of their contents into the synaptic cleft. Fusion of the synaptic vesicles with the plasma membrane is an example of regulated exocytosis, which is mediated by neuron-specific SNAREs that facilitate vesicle targeting and fusion. Neurotransmitters diffuse across the synaptic cleft and are bound by specific receptors that cluster on the surface of the postsynaptic cell. Once neurotransmitters have bound to the receptors, they will initiate a change in the membrane potential of the postsynaptic cell. Through this process of synaptic transmission, an action potential in the presynaptic cell is transmitted to the postsynaptic cell via a chemical signal.

Neurotransmitter receptors

There are two distinct types of neurotransmitter receptors that can trigger a change in the membrane potential of a postsynaptic cell: ligand-gated ion channelsand G-protein linked receptors. Ligand-gated ion channels will be described below, and in a future tutorial on cell signaling you will learn more about G-protein linked receptors. In the absence of the neurotransmitter, the ligand-gated ion channel is closed to the flow of ions. Restated, the pore that ions flow through is blocked or gated. When the receptor binds to the neurotransmitter, a conformational change is induced that allows the gate to open and ions to flow through the channel (see Figure 6). The flow of ions is rapid and brief, resulting in a change in the membrane potential. Once the ligand has bound to the receptor, it rapidly dissociates from it and the channel returns to the closed state. Normally the half-life of neurotransmitters in the synaptic cleft is very short, on the order of milliseconds. Termination of the flow of neurotransmitters ensures that the postsynaptic cell can reestablish the resting potential and be ready to receive another signal from the presynaptic cell. Clearing of the neurotransmitter from the synaptic cleft occurs in two ways: enzymatic degradation or reuptake (resorption back into the presynaptic cells by specific transporter proteins).

The Acetylcholine Receptor and the Neuromuscular Junction

One of the best-studied examples of chemical transmission is the neuromuscular junction, the synapse between a motor neuron and a skeletal muscle fiber. Synaptic transmission is mediated by the neurotransmitter acetylcholine, which is released into the synaptic cleft by the presynaptic neuron. In the synaptic cleft, acetylcholine either binds to its receptor on the postsynaptic cell or is rapidly degraded by the enzyme acetylcholinesterase. This ensures that there is only a brief response of the postsynaptic cell. The acetylcholine receptoris a relatively nonspecific ligand-gated ion channel that is open to the flow of ions only when it binds to acetylcholine. Upon binding to acetylcholine, the muscle fiber is stimulated. There is an influx of sodium ions into the postsynaptic muscle fiber and the membrane becomes depolarized, leading to an action potential, and ultimately, muscle contraction. The nerve gas sarin is a potent neurotoxin and inhibitor of acetylcholineseterase, which affects an accumulation of acetylcholine at the neuromuscular junction. The high levels of acetylcholine in the synaptic cleft lead to increased depolarization and contraction of the muscle fibers; however, without the ability to recover from stimulation, the muscle fiber is inactivated, thus leading to paralysis.

The GABA receptor and synapses in the brain

In the brain, neurons make synapses with other neurons. The number and nature of these synapses are more complex than the neuromuscular junction. Brain neurons receive inputs from many cells, and these signals can be contradictory. Some synapses can be excitatory, causing depolarization similar to the neuromuscular junction, and others can be inhibitory, reducing the chance of depolarization. The most prevalent neurotransmitter in the brain is gamma-aminobutyric acid(GABA), which is a derivative of the amino acid glutamic acid. GABA is released by the presynaptic neuron into the synaptic cleft. It is bound by the GABA receptors on the postsynaptic neuron or it is rapidly transported back into the presynaptic cells. The GABA receptor is a ligand-gated ion channel, which when open allows the flow of chloride ions into the cells. The effect of the chloride ion influx is to make the membrane potential even more negative and counteract the effect of the sodium ion influx associated with depolarization. Therefore, GABA is considered an inhibitory neurotransmitter that produces hyperpolarization in the postsynaptic cell and reduces the likelihood of an action potential in that neuron. Tranquilizers such as Valium enhance the normal effects of GABA by binding to the GABA receptor and increasing its ability to bind to GABA. Thereby, the normal level of GABA results in a greater inhibition of the postsynaptic neuron.


A neuron is an electrically excitable cell capable of generating, conducting, and transmitting electrochemical signals. A typical neuron has characteristic features: a cell body, dendrites and an axon. The axon projects from the cell body and makes contact with a target cell at the synapse. A neuron is stimulated by signals, chemical and electrical, to initiate an action potential (a rapid and reversible change in membrane potential). In the absence of a signal, the resting potential of the neuron is maintained by the potassium leak channels, which allow the flow of potassium ions out of the cell, resulting in a more negative charge in the cell when compared to outside the cell. In response to a stimulation, the neuron initiates an action potential orchestrated by the opening and closing of voltage-gated ion channels. First, depolarization of the membrane occurs when the voltage-gated sodium channels are opened and there is a large influx of sodium ions. Second, the sodium channels are rapidly inactivated and the voltage-gated potassium channels open, resulting in the efflux of potassium ions and the repolarization of the membrane. Third, the voltage-gated potassium channels close and the potassium leak channels reestablish the resting membrane potential. The action potential is propagated along the length of the axon. Each action potential in one region of the membrane triggers depolarization of the membrane further along the axon.

In the presynaptic cell, the action potential is used to generate a chemical signal for transmission across the synaptic cleft to the postsynaptic cell. The propagating action potential will trigger the opening of voltage-gated calcium channels at the terminus of the axon. The influx of calcium ions will lead to exocytosis of the synaptic vesicles, containing neurotransmitters, and the release of these neurotransmitters into the synaptic cleft. A neurotransmitter is either bound by its receptor on the membrane of the postsynaptic cell or cleared from the synaptic cleft by one of two means: degradation or reuptake. Many neurotransmitter receptors are ligand-gated ion channels that only open when they bind to a specific neurotransmitter. Some receptors are excitatory, such as the acetylcholine receptor that binds acetylcholine and allows the influx of sodium ions, thereby depolarizing the membrane and stimulating an action potential in the postsynaptic cell. Other receptors are inhibitory, such as the GABA receptor that binds GABA and allows the influx of chloride ions, thereby hyperpolarizing the membrane and inhibiting an action potential in the postsynaptic cell.