Chapter 11

Alpha receptors

alpha 1 alpha 2 located in effector organs of SNS most common usually excitatory affinity greater for norepinephrine than epinephrine

Spinal nerves

pelvic nerves are distinct from spinal nerves

Events at the neuroeffector junction

1. action potential arrives at varicosity 2. voltage gated Ca2+ channels open 3. Ca 2+ triggers exocytosis of neurotransmitter 4. . Neurotransmitter binds with receptors on effector organ 5. Response in effector organ occurs 6. Neurotransmitter is degraded and diffuses away; reuptake occurs

The enyzme that degrades acetylcholine in the synaptic cleft is called _

ACHE

4. What are the two primary neurotransmitters of the efferent branch of the peripheral nervous system, and which neuron(s) release them?

Acetylcholine and norepinephrine Cholinergic neuron releases acetylcholine Adrenergic neuron releases norepinephrine Acetylcholine is released by preganglionic neuron of both SNS and PNS and by postganglionic neuron of the parasympathetic nervous system. The sympathetic preganglionic neurons that innervate the chromaffin cells of the adrenal medulla release acetylcholine Norepinephrine is released by almost all sympathetic postganglionic neurons. Neurons that release norepinephrine are referred to as adrenergic.

signal transduction mechanism at effector organs of the sympathetic nervous system at alpha1 receptor

Adrenergic receptors are coupled to G proteins that either activate or inhibit second messenger systems. Binding of norepinephrine or epinephrine to an alpha1 receptor activates a G pro- tein, which in turn activates the enzyme phospholipase C, which then catalyzes the conversion of phosphatidylinositol bisphosphate (PIP2) to inositol triphosphate (IP3) and diacylglycerol (DAG) (Figure 11.8a). IP3 enters the cell and triggers the release of calcium from intracellular stores. Calcium then causes a response in the cell. DAG activates the enzyme protein kinase C, which catalyzes the phosphorylation of a protein, causing a re- sponse in the cell.

Describe the anatomical arrangement of the somatic nervous system, including the concept of motor units.

Answer: In the somatic nervous system, a single efferent neuron runs from the central nervous system to the skeletal muscle. These motor neurons originate in the ventral horn of the spinal cord and receive input from multiple sources, including afferent neurons. A single motor neuron innervates multiple muscle fibers but each muscle is innervated by a single neuron. A motor unit describes a single motor neuron and all of the skeletal muscle fibers innervated by that neuron. Thus, when a motor neuron is activated, all of the muscle fibers innervated by that motor neuron are stimulated to contract simultaneously.

Norepinephrine is one of the more important neurotransmitters of the peripheral nervous system. Identify the branches of the peripheral nervous system for which norepinephrine is the neurotransmitter and describe the receptors responsible for responding to norepinephrine. Include the mechanisms whereby these receptors transduce the response to norepinephrine.

Answer: Neurons that release norepinephrine are referred to as adrenergic neurons. Norepinephrine is the neurotransmitter for most postganglionic sympathetic neurons (except sympathetic neurons that innervate sweat glands). The end organ receptors for norepinephrine are classified into two majors groups: and receptors. Within each of these classes are several subclasses of receptors with different sensitivities to catecholmines (norepinephrine and epinephrine) and different links to second messenger cascades. Each of the adrenergic receptors are metabotropic and are coupled to a G protein, but the particular G protein can be different (Gs vs Gi). The 1 adrenergic receptor subtype is coupled to activation of phospholipase C for the synthesis of inositol triphosphate, while the 2 adrenergic receptor subtype acts through Gi to suppress the synthesis of cAMP. All three of the receptors are stimulatory, linked through Gs, and are involved in the activation of cAMP. Diff: 6 Page Ref: 309

Acetylcholine is one of the most common neurotransmitters in the peripheral nervous system. Identify the branches of the peripheral nervous system for which acetylcholine is the neurotransmitter and describe the receptors responsible for responding to acetylcholine. Include the mechanisms whereby these receptors transduce the response to acetylcholine.

Answer: Peripheral neurons that release the neurotransmitter acetylcholine are classified as cholinergic. Acetylcholine is released by all autonomic preganglionic fibers, postganglionic fibers of the parasympathetic nervous system, and the somatic branch of the efferent nervous system. One exception is that acetylcholine is a postganglionic sympathetic neurotransmitter for sweat glands. The two classes of cholinergic receptors are termed nicotinic (based upon the binding of this receptor to nicotine) and muscarinic (based upon the binding of this receptor to a toxic chemical in mushrooms). Nicotinic receptors are ionotropic receptors (receptor and ion channel are within the same protein) that are always excitatory. Thus, the binding of acetylcholine increases the number of open non-selective cation channels that are permeable to both sodium and potassium. The greater electrochemical gradient for sodium means that activating a nicotinic receptor will result in a depolarization of the membrane (i.e., more sodium moves in than potassium moves out). Nicotinic receptors are found on all autonomic postganglionic fibers and the end organ of the somatic nervous system (skeletal muscle). Muscarinic receptors are coupled to G proteins. Thus, these metabotropic receptors can be either inhibitory or excitatory, depending upon the target cell and the signal transduction pathway. Muscarinic receptors are found on the effector organs of the parasympathetic nervous system.

The nature of a response from the parasympathetic nervous system is determined by the anatomy of this system. Describe the anatomy of the parasympathetic nervous system and how that differs from the sympathetic nervous system.

Answer: Preganglionic neurons from the parasympathetic nervous system originate from the brainstem and the sacral region of the spinal cord (craniosacral region). The parasympathetic nerves that leave the spinal cord do not join with the spinal nerve as occurs in the sympathetic nervous system. Instead, they join with other parasympathetic preganglionic fibers to form pelvic nerves. Generally speaking, preganglionic parasympathetic nerves are long (compared with the postganglionic nerves), traveling to a ganglion that is located near the effector organ. This arrangement is quite different from the sympathetic nervous system, where most preganglionic nerves are short and enter ganglia within the sympathetic trunk. Thus, the parasympathetic nervous system is able to exert more discrete effects than the sympathetic nervous system due to the lack of interconnection between ganglia. Four parasympathetic preganglionic neurons originate from cranial nerve nuclei located within the brainstem, which explains why some preganglionic parasympathetic nerves travel within cranial nerves. The vagus nerve (X) is one of the more important parasympathetic nerves, innervating the lungs, heart, stomach, etc. The other cranial nerves that contain preganglionic parasympathetic axons are the oculomotor (III), facial (VII), and glossopharyngeal nerves (IX).

1) The nature of a response from the sympathetic nervous system is determined by the anatomy of this system. Describe the general structure of the sympathetic nervous system, including the three anatomical configurations and how they contribute to the overall sympathetic response.

Answer: The efferent pathway of the sympathetic nervous system is composed of two neurons, connected in series, that provide for communication between the central nervous system and the effector organ. Those neurons communicate with one another by synapsing within autonomic ganglia. The neurons that travel from the central nervous system to the sympathetic ganglia are the preganglionic neurons, while those that travel from the ganglia to the effector organ are the postganglionic neurons. The preganglionic neurons of the sympathetic nervous system emerge from the lateral horn of the spinal cord within the thoracic and lumbar (thoracolumbar) regions, and exit from the ventral root. The dorsal and ventral roots combine to form the spinal nerve. Thereafter, the organization of the sympathetic nervous system can be described in three ways, based upon anatomical differences. First, the most common arrangement involves a short preganglionic neuron (compared to the postganglionic neuron) that leaves the spinal nerve via a branch called the white ramus and enters one of several sympathetic ganglia. These ganglia are linked together to form a structure that parallels the spinal cord within the sympathetic chain. After entering the sympathetic chain, a preganglionic neuron may branch into several collateral axons that travel up and down the sympathetic trunk to synapse with other postganglionic neurons. Each of these postganglionic neurons travels to a particular effector organ. Thus, activation of the sympathetic nervous system typically produces a response that is widespread, affecting multiple organs simultaneously. The second anatomical arrangement of the sympathetic nervous system contains a long preganglionic fiber that innervates the adrenal medulla. In this case, the chromaffin cells of the adrenal medulla act as the postganglionic neuron. When stimulated, chromaffin cells release catecholamines into the blood (80% epinephrine, 20% norepinephrine, and trace amount of dopamine). This architecture reinforces the widespread effect of the sympathetic nervous system on the body. The final anatomical arrangement contains preganglionic neurons that synapse with postganglionic fibers in collateral ganglia located outside of the sympathetic trunk. One example is a ganglion within the digestive system called the celiac ganglion, which is innervated by a long preganglionic neuron and is located outside of the sympathetic trunk. This arrangement provides for some very specific activity particular to organs, although this type of arrangement is uncommon.

Describe the synaptic junctions between the neurons of the autonomic and somatic nervous systems and their effector organs.

Answer: The neuroeffector junction describes the synapse between neurons of the autonomic nervous system and their effector organs. The anatomy of these structures is quite different from the typical neuron-neuron synapse. The postganglionic neuron does not have a discrete, well-defined axon terminal. Rather, those neurons contain numerous swellings along their length (varicosities). Within those varicosities, neurotransmitters (norepinephrine and acetylcholine) are synthesized and stored in vesicles, as occurs at axon terminals. However, while the swellings contain the voltage-gated calcium channels that are required for the release of neurotransmitter, they also contain the voltage-gated sodium and potassium channels that are required for the propagation of an action potential along the length of the axon. At the same time, the distance between a varicosity and the postsynaptic membrane is greater than what is observed in the synaptic cleft of other synapses. In the somatic nervous system, the synapse (neuromuscular junction) couples the motor neuron to skeletal muscle fibers. The terminal bouton of the motor neuron contains acetylcholine stored in vesicles. The motor end plate is a specialized region of the skeletal muscle that contains an invagination where nicotinic receptors are located. Surrounding this invagination are local regions of high acetylcholinesterase concentration.

Location of cholinergic receptors

Autonomic postganglionic = nicotinic cholinergic Effector organ for parasympathetic = muscarinic cholinergic Skeletal muscle = nicotinic cholinergic

signal transduction at alpha 2 receptor

Binding of norepinephrine or epinephrine to an alpha 2 receptor activates an inhibitory G protein (Gi) that decreases the activity of the enzyme adenylate cyclase, thereby suppressing the synthesis of cAMP (Figure 11.8b). Binding of norepinephrine or epi- nephrine to a receptor, by contrast, activates a stimulatory G protein (Gs) that increases the activity of the enzyme adenylate cyclase, thereby enhancing the synthesis of cAMP (Figure 11.8b).

Autonomic ganglia

Communication from preganglionic to postganglionic neuron • Intrinsic neurons

Compare the anatomical pathways for innervation of effector organs by the sympathetic and parasympathetic branches of the autonomic nervous system.

Dual Innervation of the Autonomic Nervous System Both divisions of the autonomic nervous system innervate most effector organs Primary function: regulate organs to maintain homeostasis Parasympathetic and sympathetic activities tend to be antagonistic Parasympathetic nervous system: rest Sympathetic nervous system: fight-or-flight response

Properties of β2 adrenergic receptors

Located in some blood vessels and smooth muscle • Usuallyinhibitory • Greater affinity for epinephrine than norepinephrine

6. What are visceral reflexes, and how are they involved in the control of autonomic functions?

Most changes in the activity of the autonomic nervous system are accomplished through the visceral reflexes—automatic changes in the functions of organs that occur in response to changing conditions within the body. Consider, for example, the autonomic response that operates when a person stands up rapidly (Figure 11.11). The drop in blood pres- sure that occurs because blood pools in the lower limbs due to the force of gravity is detected by receptors in some of the major arteries (aorta and carotid arteries); this information is then relayed to cardiovascular regulatory areas in the medulla oblongata through an afferent pathway. In response, these areas adjust their output to the sympathetic and parasympathetic nervous systems. Sympathetic output to the heart and blood vessels is enhanced, which brings blood pressure back to normal. At the same time, parasympathetic output to the heart decreases, which allows the blood pressure to increase unopposed.

16. Which enzyme catalyzes the formation of diacylglycerol and inositol triphosphate? .

Phospholipase C

Sympathetic pathways to and from the sympathetic chain

Preganglionic Exits via the ventral root of the spinal cod and enters the spinal nerve Axons leave the spinal nerve as white ramus and enter sympathetic ganglia Exception: collateral ganglia Communicate in ganglia with postganglionic neurons

Parasympathetic nervous system

REST and DIGEST quiet relaxed states active in rest and digest increase gastrointestinal activities decreases heart rate and blood pressure

properties of Beta adrenergic receptors

all activate cAMP affinities for norepinephrine and epinephrine varies

3. Which part of the autonomic nervous system—sympathetic or parasympathetic—produces the more diffuse response? Why?

Sympathetic because the ganglia are not interconnected => providing routes that enable the sympathetic nervous system to selectively target organs and produce more discrete effects

2. Which autonomic division regulates the release of epinephrine from the adrenal medulla?

Sympathetic division

Which neurons in the peripheral nervous system are adrenergic?

Sympathetic postganglionic neuron

Neuromuscular junction

Synapse between a motor neuron and a muscle fiber The synapse between an efferent neuron and its effector organ is called a neuroeffec- tor junction • Anatomy of the neuromuscular junction Terminal bouton = axon terminal • Motor end plate=specialized muscle membrane at junction • All motor neurons release acetylcholine • Nicotiniccholinergicreceptors • Synapsesareexcitatory • Acetylcholinesterase

What is a neuroeffector junction? In which respects are autonomic neuroeffector junctions different from ordinary neuron to-neuron synapses? In which respects are they the same?

The synapse between an efferent neuron and its effector organ is called a neuroeffector junction Differences Synapses between autonomic postganglionic neurons and their effector organs differ from ordinary neuron-to- neuron synapses in that the postganglionic neurons do not have discrete axon terminals. Similarities The mechanism of neurotransmitter release from these varicosities is similar to the mechanism of transmitter release from an ordinary axon terminal (Figure 11.10). An action potential arriving at a varicosity opens voltage-gated calcium channels, which then allows calcium to enter the cytosol and stimulates the release of neurotransmitter by exocytosis First, because a single postganglionic axon has several varicosities, an action potential propagated along the axon triggers the release of neurotransmitter from all of the varicosities. Second, because the distance between the varicosity and effector organ is greater than the width of a synaptic cleft, the neurotransmitter released from a varicosity diffuses over a greater area of the effector organ, binding to receptors on cells throughout the effector organ.

Types of adrenergic receptors

Two main classes = alpha and beta Each has subclasses All are coupled to G proteins

All autonomic Preganglion neuron releases

acetylcholine

Cholinergic receptor

acetylcholine

Parasympathetic postganglion neurons releases

acetylcholine

visceral reflexes

automatic changes in the functions of organs that oc- cur in response to changing conditions within the body.

Preganglionic neurons of the parasympathetic nervous system originate in the ____________ or __________ spinal cord

brainstem and sacral Long preganglionic neuron to ganglia near the effector organ Preganglionic neuron communicates with the postganglionic neuron in ganglia Short postganglionic neuron from ganglia to effector organs

effector organs

cardiac muscle, smooth muscle, glands, adipose tissue

Adrenergic receptors have a greater affinity for (epinephrine/norepinephrine)

epinephrine

cranial nerve VII

facial nerve

13. Autonomic nerves contain only efferent neurons. (true/false)

false

Sympathetic nervous system:fight-or-flight response

fight or flight • Prepares for emergency, stress, and exercise • Increases heart rate and blood pressure • Mobilizes energy stores • Dilates pupils • Decreases gastrointestinal and urinary functions

cranial nerve IX

glossopharyngeal nerve

7. Which areas of the CNS exert primary control over the autonomic nervous system?

hypothalamus, pons, and medulla oblongata

nicotinic cholinergic receptors

ionotropic cause cation channels to open channel opening results in depolarization (excitatory)

Properties of β3 adrenergic receptors

located in adipose tissue usually excitatory equal affinity for norepinehrine and epinephrine

properties of Beta 1 adrenergic receptors

located in cardiac muscle and kidneys usually excitatory equal affinity for norepinephrine and epinephrine

Which part of the adrenal gland secretes epinephrine?

medulla

Muscarinic cholinergic receptors

metabotropic G-protein coupled effect depends on target cell

Chromaffin cells

modified sympathetic post ganglion cells Synthesized 80% epinephrine 20% norepinephrine, <1% dopamine

Both divisions of the autonomic nervous system innervate __________________ organs What is the primary function? Parasympathetic and sympathetic activities tend to be ____________________

most effector Regulate organs to maintain homeostasis antagonistic

18. The motor end plate has (nicotinic/mus- carinic) cholinergic receptors.

nicotinic

Adrenergic receptors

norepinephrine

sympathetic postganglionic neurons releases

norepinephrine

varicosities

numerous swellings located at intervals located at intervals along the axons of these neurons. where neurotransmitters are synthesized and then stored in vesicles and released

Cranial nerve III

oculomotor

collateral ganglia

outside the sympathetic chain Within the collateral ganglion, the pregangli- onic neuron forms synapses with several postganglionic neurons that travel to target tissues. situated somewhere between the CNS and the effector organ

Which neurons in the peripheral nervous system are cholinergic?

parasympathetic preganglionic and postganglionic neurons, sympathetic preganglionic neuron and motor neuron

two types of neurons from CNS to effector organs

pre ganglion neurons post ganglion neurons

Anatomy of the SNS

the preganglionic neurons originate in the thoracolumbar spinal cord -lateral horn Short preganglion neurons to sympathetic chain Long postganglion neurons from sympathetic chain to effector organs Ganglia linked together in sympathetic chain

Skeletal muscle can be excited to contract only; that is, it cannot be inhibited to relax.

true

Cranial nerve X

vagus nerve

12. Name the four cranial nerves that contain parasympathetic preganglionic neurons.

vagus nerve Oculomotor nerve facial nerve glassopharyngeal nerve

Anatomy of Somatic nervous system

• Originate ventral horn • Innervate skeletal muscle • Neurotransmitter=acetylcholine • Receptors in skeletal muscle=nicotinic cholinergic