Bio 12.2 Neural Communication PDF

Enter word / phrase to search UBook text Automatic ZoomActual SizePage Width100%50%75%100%125%150%200%300%400% Chapter 12: Nervous System 424 Lesson 12.2 **Neural Communication** Introduction Neural communication with other cells (eg, other neurons, myocytes) is enabled by special neuronal im...

Enter word / phrase to search UBook text Automatic ZoomActual SizePage Width100%50%75%100%125%150%200%300%400% Chapter 12: Nervous System 424 Lesson 12.2 **Neural Communication** Introduction Neural communication with other cells (eg, other neurons, myocytes) is enabled by special neuronal impulses called **action potentials** that cause a temporary reversal of the charge gradient at their axon terminals. This lesson first discusses the electrical gradient present in neurons under unstimulated conditions, called the resting membrane potential, before presenting the mechanisms by which action potentials are generated and elicit responses in target cells. 12.2.01 Resting Membrane Potential [Phospholipid bilayers](javascript:void(0)) are not very permeable to charged molecules, so ion transport in and out of cells occurs predominantly via proteins embedded in the cell membrane (see Lesson 5.2). For example, channels allow ions to diffuse across the plasma membrane, whereas pumps use energy to move ions across the membrane. Because of the various types, numbers, and activities of the membrane transport proteins, cell plasma membranes are [selectively permeable](javascript:void(0)). As a result of this selective permeability, concentrations of charged molecules in the intracellular and extracellular fluid differ, and electrical and concentration gradients exist. The concentration gradients of the various ions favor the movement of the ions from areas of higher concentration to areas of lower concentration, whereas the electrical gradient across the plasma membrane attracts ions to oppositely charged regions, as depicted in Figure 12.6. **Figure 12.6** The effect of chemical and electrical gradients on ions. Because opposite charges attract, the separation of charge across the cell membrane represents a form of potential energy that can be used to drive cellular processes (eg, secondary active transport), and the magnitude of the charge difference is accordingly called the **membrane potential**. By convention, the membrane potential is measured using the extracellular fluid as a reference (assigned a value of 0 mV). A diagram of a cell Description automatically generated with medium confidence Chapter 12: Nervous System 425 In a cell at rest, the membrane electrical polarization is such that the intracellular fluid is typically more negative than the extracellular fluid. If only a single ion type could cross a plasma membrane, that ion\'s movement would be influenced by both its concentration gradient (favoring movement from higher to lower concentration) and the membrane\'s electrical gradient (favoring movement away from like charges and toward opposite charges). For a given concentration gradient, there is an electrical gradient that would exactly oppose the concentration gradient and prevent net ion movement across the membrane. This membrane potential, at which the ion\'s concentration and electrical gradients cancel each other, is called the ion\'s **equilibrium potential** (Figure 12.7). **Figure 12.7** Equilibrium potential. Because both electrical and concentration (ie, chemical) gradients influence ionic movement across the plasma membrane, the combined influence is referred to as the **electrochemical gradient**. Ions diffuse across cellular membranes down the ion\'s electrochemical gradient. In an actual cell, the plasma membrane is permeable to more than one ion, so the electrochemical gradients of multiple ions simultaneously influence the cell\'s membrane potential. Ions with greater permeability exert a greater influence on the membrane potential, pushing the membrane potential in the direction of the equilibrium potential of these more permeable ions. The **resting membrane potential (RMP)** is the electrical gradient across a cell\'s membrane under baseline (unstimulated) conditions. Although numerous ions can cross the plasma membrane, Na+ and K+ play a major role in establishing the RMP (Figure 12.8). Leak channels for each ion allow a small, continual stream of the two ions across the plasma membrane via diffusion, and Na+/K+ ATPase pumps the ions back across the plasma membrane against their concentration gradients. The net result of transport through these and other membrane proteins is that the plasma membrane is \~40 times more permeable to K+ than to Na+. Accordingly, the RMP of approximately −70 mV is closer to the equilibrium potential of K+ (−90 mV) than that of Na+ (+60 mV).  Chapter 12: Nervous System 426 **Figure 12.8** Primary determinants of the resting membrane potential. 12.2.02 The Action Potential Just as the combination of open and closed channels determines the resting membrane potential (RMP), a change in the complement of open and closed channels in a cell\'s membrane can alter the cell\'s membrane potential. An **action potential** is a brief, regenerative wave of membrane potential fluctuation that travels away from the site of initiation in an excitable cell (eg, neuron, muscle). In neurons, action potentials originate from a region called the **trigger zone**, consisting of the axon hillock and the initial part of the axon, when the trigger zone membrane potential becomes more positive than a certain threshold (around −55 mV). In addition to its use to describe these electrical impulses that travel long distances, the term *action potential* is used to denote the stereotypic pattern of membrane potential changes that occur in a single location during one of these electrical impulses. These changes include a period of **depolarization** (ie, in which the membrane potential becomes more positive) followed by a period of **repolarization** (ie, in which the membrane potential returns to its baseline level). Figure 12.9 depicts these membrane potential changes in a neuron and a muscle cell membrane. A diagram of a cell Description automatically generated Chapter 12: Nervous System 427 **Figure 12.9** The characteristic pattern of membrane potential depolarization and repolarization that occurs during an action potential. The use of the term *action potential* to describe both the electrical impulse moving along a cell\'s membrane, as well as the characteristic local membrane potential changes accompanying such a signal, alludes to an important point: The moving electrical impulse is composed of multiple isolated events. By analogy, a \"wave\" in a stadium consists of multiple sections of people standing and sitting in sequence  Chapter 12: Nervous System 428 (not one set of people running around the stadium). Similarly, the regenerating depolarization wave that travels along the membrane during an action potential consists of ion channels in multiple membrane regions being activated sequentially (Figure 12.10). **Figure 12.10** Like a wave in a stadium, the large-scale action potential that travels down an axon consists of multiple, local events in sequence. As with the RMP, the movement of sodium (Na+) and potassium (K+) ions is responsible primarily for the fluctuations in membrane potential that occur during an action potential. The changes in ion concentrations underlying a single action potential are very small and do not affect the overall Na+ and K+ concentration gradients across the cell membrane. However, this ion movement does affect the electrical gradient, as manifested in membrane potential changes. During an action potential, **voltage-gated** **channels** for Na+ and K+ (Figure 12.11) play essential roles, as do the Na+ and K+ leak channels that contribute to the RMP (see Concept 12.2.01). Voltage-gated Na+ A diagram of a stadium Description automatically generated Chapter 12: Nervous System 429 and K+ channels both have a structural component called an **activation gate** that opens to allow ion flow through the channel in response to depolarization. The voltage-gated Na+ channel also possesses a second, **inactivation gate** that closes in response to depolarization. Note that the naming of these gates varies across sources, but this is how they will be referred to in this book. **Figure 12.11** Voltage-gated Na+ and K+ channels. The rates at which these gates open and close are very important, and Na+ activation gates open before the movements of the other gates are completed. An action potential encompasses three phases: 1.A **rising phase** in which the membrane potential becomes progressively more positive 2.A **falling phase** in which the membrane potential becomes progressively more negative, eventually becoming hyperpolarized 3.A **restoring phase** in which the membrane potential returns to the resting level from a hyperpolarized state In the rising phase (Figure 12.12), the membrane potential becomes more positive due to increased Na+ permeability caused by the opening of Na+ channel activation gates. Depolarization to the **threshold potential** (around −55 mV) is pivotal because this initiates a [positive feedback cycle](javascript:void(0)) of depolarization-induced Na+ channel opening, leading to further depolarization. Eventually, this feedback cycle leads to the activation of all the voltage-gated Na+ channels in the vicinity. Therefore, if the threshold potential is reached, an action potential occurs, and, if the threshold is not reached, an action potential does not occur (ie, action potentials are **\"all-or-none\"** events).  Chapter 12: Nervous System 430 **Figure 12.12** The rising phase of the action potential. In response to the influx of positively charged Na+ into the intracellular fluid, the inside of the cell becomes more positive and the extracellular fluid more negative. Because of this Na+ influx, the membrane potential eventually reverses sign, becoming positive, and peaks at a membrane potential of around +40 mV. The part of the action potential above 0 mV is sometimes called **overshoot**. After the peak of the rising phase, the membrane potential begins the sharp decline of the falling phase (Figure 12.13). To start this phase, voltage-gated Na+ channel inactivation gates close, thereby ending the inward flow of Na+. At the same time, voltage-gated K+ channels open, reversing and eventually hyperpolarizing the membrane (ie, becoming more negative than the RMP). As membrane potential falls Diagram of a cell structure Description automatically generated with medium confidence Chapter 12: Nervous System 431 below the threshold potential, Na+ channels begin resetting to the resting state. The portion of the action potential more negative than the RMP is sometimes called **undershoot**. **Figure 12.13** The falling phase of the action potential. For most of the falling phase, the voltage-gated Na+ channels are closed, primarily via the inactivation gates, and the voltage-gated K+ channels are open, neither of which occur during the resting state. The restoring phase (Figure 12.14) of the action potential occurs when voltage-gated Na+ and K+ channels are finished being reset to the resting state and the RMP is restored. In this phase, the Na+ channel activation gates return to the closed position while the inactivation gates return to the open position. At the same time, voltage-gated K+ channels close. With closure of the voltage-gated Na+ and K+ channels, Na+ and K+ leak channels, along with the Na+/K+ pump, are of primary importance in  Chapter 12: Nervous System 432 determining membrane potential, and membrane potential rises back to the RMP (approximately −70 mV). **Figure 12.14** The restoring phase of the action potential. The complete action potential is shown in Figure 12.15. A diagram of a diagram of a contraceptive Description automatically generated with medium confidence Chapter 12: Nervous System 433 **Figure 12.15** The action potential. The excitability of a neuron changes during the action potential. As the rising membrane potential exceeds the threshold potential, all Na+ channels become committed to opening. As the membrane potential begins falling, Na+ channels are closed via the inactivation gates, a state incompatible with channel opening. With no Na+ channels available for activation, the neuron enters an **absolute refractory period** during which no amount of stimulation can elicit an action potential. This delayed return of excitability after the depolarization phase of an action potential ensures unidirectional flow along the axon. After the absolute refractory period, the Na+ channels begin resetting to the resting state (ie, activation gates close and inactivation gates open). As this occurs, the neuron enters a **relative refractory period** that continues until the Na+ and K+ channels return to their resting states and the RMP is restored. During this period, newly reset Na+ channels can be recruited to open, provided that the depolarizing stimulus is stronger than normal. A stronger stimulus is necessary to overcome the influence of open K+ channels (early in the period), as well as the hyperpolarized membrane potential.  Chapter 12: Nervous System 434 **Concept Check 12.2** Identify the status (ie, open or closed) of voltage-gated Na+ and K+ channels for each of the following phases in a typical action potential: the rising portion of the overshoot, the falling portion of the overshoot, the falling portion of the undershoot, the rising portion of the undershoot. [**Solution**](javascript:void(0)) 12.2.03 Synaptic Transmission Neurons communicate via junctions called **synapses** that are sites of actual or near contact between a neuron and another cell (either another neuron or a cell in a target tissue such as skeletal muscle). Communication between the two cells is directional, with the nerve impulse in the **presynaptic** (transmitting) neuron being communicated to the **postsynaptic** (receiving) cell. Synapses consist of the axon terminal of the presynaptic neuron and the plasma membrane of the postsynaptic cell, as well as the space between the two cells when the cells are not in direct contact. In a synapse between two neurons, the nerve impulse is typically transmitted from the presynaptic axon terminal to a postsynaptic dendrite or soma, as shown in Figure 12.16. **Figure 12.16** A synapse between two neurons. Synaptic transmission of a nerve impulse between neurons can occur via an electrical or a chemical mechanism (Figure 12.17). At **electrical synapses**, electrical impulses are transmitted directly from one cell to the other via gap junctions. At **chemical synapses**, ligands called **neurotransmitters** are released from the presynaptic neuron into the **synaptic cleft** (ie, the space between the presynaptic axon terminal and the postsynaptic cell). The neurotransmitters bind postsynaptic membrane receptors, which often causes postsynaptic ligand-gated ion channels to open, facilitating ion movement into or out of the postsynaptic cell. A blue check mark in a square Description automatically generated  Chapter 12: Nervous System 435 **Figure 12.17** Electrical versus chemical synapses. The signal from the presynaptic neuron is diminished or terminated in a chemical synapse when the concentration of neurotransmitter in the synaptic cleft is reduced. In some cases, this occurs through [simple diffusion](javascript:void(0)) of the neurotransmitter away from the synapse. In other cases, neurotransmitter levels are reduced via reuptake into the presynaptic neuron or through enzymatic destruction. 12.2.04 Neurotransmitters **Neurotransmitters**, the signaling molecules released from presynaptic neurons at chemical synapses, can elicit a variety of responses in postsynaptic cells. In nearly all cases, these responses are initiated by neurotransmitters binding to receptors on the postsynaptic cell membrane, which influences the membrane potential of the postsynaptic neuron. Neurotransmitters and the synapses at which they act are classified as excitatory or inhibitory based on their effect on the postsynaptic membrane potential. **Excitatory neurotransmitters** have a *depolarizing* effect on the postsynaptic membrane (ie, cause the membrane potential to become more positive, often in response to positive ions such as Ca2+ entering the A diagram of a synapse Description automatically generated Chapter 12: Nervous System 436 neuron), as shown in Figure 12.18. If the membrane potential of the postsynaptic neuron at an excitatory synapse exceeds a certain threshold (approximately −55 mV), an action potential is initiated in the postsynaptic neuron (see Concept 12.2.02). **Figure 12.18** Synaptic transmission involving excitatory neurotransmitters. The binding of **inhibitory neurotransmitters** to the postsynaptic neuron causes either an influx of negative ions (eg, Cl−) or an efflux of positive ions (eg, K+). In both cases, binding of the inhibitory neurotransmitter causes the cell\'s membrane potential to become more negative (ie, **hyperpolarize**), inhibiting action potential initiation, as shown in Figure 12.19.  Chapter 12: Nervous System 437 **Figure 12.19** Synaptic transmission involving inhibitory neurotransmitters. As noted previously, most neurotransmitters act through binding to postsynaptic receptors. Table 12.1 presents several neurotransmitters and their functions. A diagram of a neuron Description automatically generated Chapter 12: Nervous System 438 **Table 12.1** Common neurotransmitters and their functions. **Neurotransmitter** **Functions** Glutamate (Glu) Primary excitatory neurotransmitter of the central nervous system Involved in learning and memory Gamma-aminobutyric acid (GABA) Primary inhibitory neurotransmitter of the brain Amino acids Glycine (Gly) Primary inhibitory neurotransmitter of the spinal cord Dopamine (DA) Involved in cognition, attention, movement, reward Serotonin (5-HT) Involved in sleep, appetite, mood Epinephrine Involved in sympathetic signaling in the autonomic nervous system Norepinephrine (NE) Involved in sympathetic signaling in the autonomic nervous system Amines Acetylcholine (ACh) Involved in parasympathetic signaling in the autonomic nervous system Released by motor neurons at NMJs of the somatic nervous system to excite skeletal muscle Peptides Endorphins Opiates produced by the body that modulate pain, as well as contribute to elevated mood following exercise **NMJ** = neuromuscular junction. 12.2.05 Summation of Postsynaptic Potentials As discussed in Concept 12.2.02, action potentials are \"all-or-none\" events, and, when triggered, an action potential is regenerated down an axon by the opening of new channels, such that the action potential strength is maintained. However, for an action potential to be triggered, the soma of the neuron must be depolarized to a great enough extent that the membrane potential in the trigger zone is more positive than the threshold potential. In contrast to axons, dendrites and cell bodies do not generate action potentials. Instead, the postsynaptic cell membrane potential in these areas responds incrementally, and the response is called a **graded potential** because it is proportional to the strength of the stimulus from the presynaptic cell. Graded potentials dissipate as they travel from a synapse through the cell body. Graded potentials are called **excitatory** when they depolarize the postsynaptic neuron (bringing it closer to the threshold potential) and **inhibitory** when they hyperpolarize the postsynaptic neuron (taking it farther from the threshold potential). Most postsynaptic neurons have multiple synapses, and a single presynaptic action potential typically produces only a postsynaptic graded potential (without an accompanying action potential). As a result, postsynaptic neuron behavior typically reflects the net influence of multiple presynaptic action potentials. The integration of multiple inputs from one or more presynaptic neurons is called **summation**. As shown in Figure 12.20, **spatial summation** is the integrated effect of multiple input signals from multiple presynaptic neurons, whereas **temporal summation** is the integrated effect from multiple input signals from a single neuron Some presynaptic neurons can release more than one type of neurotransmitter under the right circumstances; such neurons are called multi-transmitter neurons. In some cases, the different neurotransmitters are released from distinct vesicles (a phenomenon called co-transmission), either from the same axon terminal or from different axon branches. In other cases, two or more neurotransmitters are released from the same vesicle (a phenomenon called co-release). Summation incorporates the overall influence of the number and types of neurotransmitters acting on a postsynaptic neuron. At an **excitatory synapse**, the overall effect of the various neurotransmitters to which the postsynaptic neuron is exposed is depolarizing. At an **inhibitory synapse**, the overall effect is hyperpolarizing. Whether or not summation produces an action potential in a postsynaptic neuron is determined by the effect on the trigger zone. If a membrane potential more positive than the threshold potential (ie, a suprathreshold potential) is elicited at the trigger zone as a result of summation, an action potential will be produced. If summation produces only a graded potential or a suprathreshold potential that dissipates to a level below the threshold potential by the time it reaches the trigger zone, an action potential will not be generated.