Autonomic Nervous System

Question 1

ANS functions

Answer 1

. Innervates smooth muscle, heart and glands
. AP in nerve can result in excitation or inhibition of effector cells
. Autonomic reflexes control organ function
. 2 neurons btw CNS and effector organ
. Slower conduction: longer, less focused response

Question 2

SNS functions

Answer 2

. Innervates skeletal muscle 
. AP in nerve always results in contraction of skeletal muscle 
. Under voluntary control 
. 1 neuron btw CNS and muscle 
. Faster conduction, focused response

Question 3

ANS divisions

Answer 3

. sympathetic
. Parasympathetic
. Enteric
. Maintain homeostasis

Question 4

Single innervation target organs

Answer 4

. Sweat glands 
. Peripheral blood vessels 
. Hair follicles 
. Brown adipose 
. Adrenal medulla 
. Kidney

Question 5

Dual innervation target organs

Answer 5

. Eye 
. Salivary glands
. Lung
. Heart
. Enteric nervous system 
. Pancreas
. Liver
. Bladder
. Reproductive organs 
. Blood vessels of external genitalia

Question 6

SNS

Answer 6

. Thoracolumbar
. Preganglionic axons leave in ventral root, enter paravertebral ganglion through white rami
. Go through paravertebral or prevertebral ganglia (1 plexus in front of aorta)
. Preganglionic fibers synpase w/ postganglionic neurons or travel for several segments before forming synapses w/ postganglionic neurons
. Postganglionic axons leave ganglia through gray communicating rami to enter spinal n.
. Prevertebral plexus forms by celiac, sup., and inf. Mesenteric ganglia

Question 7

PNS

Answer 7

. Craniosacral
. Preganglionic cell bodies in nuclei of brain stem and S2-4
. Preganglionic fibers from upper nuclei distribute w/ 4 cranial nn (III, VII, IX, and X) and from sacral segments go w/ sacral nn.

Question 8

Autonomic reflexes

Answer 8

. Afferent neurons activated by stimulus
. Afferent signal integrated in CNA
. Efferent autonomic neurons activated to modulate target organ function in response to initial stimulus
. Afferent and efferent neurons may innervates the same or different organs
. Efferent arm has preganglionic (in peripheral ganglia) and postganglionic neuron (to target organs w/ varicosities along it’s length to release neurotransmitter)

Question 9

PNS functions

Answer 9

. Contract pupil 
. Inc. secretions 
. Enhance GI motility
. Stimulate insulin release 
. Slow HR
. Constrict airway 
. Vasodilate vessels

Question 10

SNS functions

Answer 10

. Dilate pupil 
. Dec. GI motility 
. Stimulate gluconeogenesis, inhibit insulin
. Inc. HR
. Inc. arterial pressure 
. Dilate bronchial smooth muscle 
. Inc. blood flow to muscle, dec. blood to abdominal organs 
. Whole body sweating

Question 11

ACh neurotransmitters

Answer 11

. Cholinergic nn.
. All sympathetic and parasympathetic preganglionic nn.
. Only sympathetic sweat gland postganglionic
. All parasympathetic postganglionic

Question 12

NE neurotransmitter

Answer 12

. Adrenergic
. All sympathetic postganglionic except sweat glands
. Adrenal medulla releases some into bloodstream

Question 13

epinephrine

Answer 13

. Released from adrenal medulla after activation of SNS

. Catecholamine

Question 14

ACh synthesis

Answer 14

. Choline + acetate -> acetyl CoA + CoA -> ACh

Question 15

NE synthesis

Answer 15

. Tyr -> DOPA -> dopamine -> NE -> E

Question 16

Characteristics of receptor-neurotransmitter interaction

Answer 16

. Threshold: conc. Of NT where response 1st occurs
. Saturation
. Specificity
. Sensitivity: conc. NT to elicit 50% max response
. Potency: ligand conc. To achieve max response
. Competition
. Agonist
. Antagonist

Question 17

Magnitude of biological response to a ligand depends on ____

Answer 17

Number of ligand-receptor complexes

. Formation is non-covalent and follows 1st order molecular kinetics

Question 18

Affinity constant K

Answer 18

. Represents how readily ligand assoc. w/ receptor
. K = [LR]/[L][R]
. K = concentration of ligand when 50% receptor sites are bound
. Lower the K, higher the affinity to receptor

Question 19

Alpha-1 adrenergic receptors

Answer 19

. Coupled to Gq protein, phospholipase C-IP3-mediated Ca signaling
. Cardiovascular: vascular smooth muscle contraction
. GI: dec. rate and strength of smooth muscle contractions (mediated by cAMP PKA dependent activation of K channels)
. Eye: dilation of pupil (mydriasis

Question 20

Alpha-2 adrenergic receptors

Answer 20

. Coupled to Gi protein, alpha subunit, dec. adenylate cyclase, cAMP, PKA
. Gi protein beta-gamma subunits inc. K channels
. Endocrine: stimulate gluconeogenesis, dec. insulin, inc. glucagon release
. GI: dec. rate and strength of smooth m. Contraction (mediated by Gi protein-induced reduction of cAMP
. CNS: located in presynaptic terminals as autoreceptors mediated neg. feedback of NE release (presynaptic inhibition)

Question 21

Beta adrenergic receptors

Answer 21

. Coupled to Gs protein
. Inc. adenylate cyclase
. Inc. cAMP
. Inc. PKA

Question 22

Beta-1 adrenergic receptors effect on systems

Answer 22

. Cardiovascular: inc. CO, HR, and contractile force of heart
. GI: inc. secretion thick viscous saliva

Question 23

Beta-2 adrenergic receptor effect on system

Answer 23

. Respiratory: dilation of bronchial smooth m. To open airways
. GI: dec. motility of visceral smooth muscle
. Endocrine: inc. glycogenolysis in adipose tissue

Question 24

Cholinergic receptors

Answer 24

. ACh receptors
. Muscarinic
. Nicotinic

Question 25

Muscarinic receptors

Answer 25

. Located on target organs . M1-M5 . Activation produces excitatory or inhibitory response depending on target organ . Activation of odd-numbered receptors leads to inc. intracellular Ca through IP3-DAG system . Activation of even numbered receptors dec. cAMP and PKA

Question 26

Muscarinic receptors effect on systems

Answer 26

. Eye: contraction of pupil (miosis) . Cardiovascular: SA node (dec. HR by M2-mediated activation of K channels), vasodilation of vessels . Respiratory: constriction bronchial smooth muscle . GI: inc. secretion thin saliva, inc. motility, inc. secretion of digestive enzymes . Endocrine: inc. insulin secretion, inc. glycogen storage . Sweat: inc. sweat . Renal: contract bladder wall during urination

Question 27

Nicotinic receptors

Answer 27

. Always produces excitatory response in skeletal m. Or autonomic neuron . Nicotinic-muscle (Nm/N1) . Nicotinic-neural (Nn/N2)

Question 28

N1 receptors

Answer 28

. at motor end plate on skeletal muscle | . Voluntary contraction of skeletal m.

Question 29

N2 receptors

Answer 29

. Located on cell bodies of all postganglionic neurons (sympathetic and parasympathetic) . Located in adrenal medulla . Activation of postganglionic sympathetic and parasympathetic neurons . Antagonists block synaptic transmission in sympathetic and parasympathetic nervous systems

Question 30

Signal transduction

Answer 30

. Neurotransmitters are hydrophilic and need receptor to cross lipid membrane . Binding to receptor triggers series of events in cell that cause biological response

Question 31

Signal amplification

Answer 31

. Single activated enzyme can turn substrate molecules into product . At each step, another application takes place . Explains how neurotransmitters can be effective at extremely low concentration

Question 32

Types of signal transduction

Answer 32

. Receptors that are also ion channels . Receptors that are protein kinases . Receptors that interact w/ JAK kinases . Receptors that are G protein coupled

Question 33

Receptors that are also on ion channels

Answer 33

. When NT binds to receptor, ion channel opens . Permits diffusion of ion down their concentration gradient . Ions entering cell can alter membrane potential and/or act as second messenger itself . Generate biological response

Question 34

Receptors that are protein kinases

Answer 34

. Most commonly tyrosine kinase | . Protein phosphorylated by tyrosine kinase generates biological response

Question 35

Receptors that interact w/ JAK kinases

Answer 35

. Binding of ligand to receptor activates JAK . JAK phosphorylated specific proteins . Generates biological response

Question 36

Receptors that are coupled to G proteins

Answer 36

. Binding of NT to receptor activates G protein by substituting GTP for GDP . Activated G protein binds to and opens ion channels or activates (or inhibits) a membrane bound enzyme . Enzyme inc. or dec. generation of 2nd messenger inside cell .2nd messenger activates a protein kinase that phosphorylates specific proteins that generate biological response

Question 37

Main second messengers

Answer 37

``` .cAMP .cGMP . IP3 . DAG . Ca (Ca-calmodulin) ```

Question 38

Cyclic AMP pathway

Answer 38

. G-binding regulatory protein (Gs) activates adenylyl cyclase (Gi inhibits adenylyl cyclase) . Adenylyl cyclase converts Mg-ATP to cAMP . Hydrolysis of GTP to GDP terminates activation .cAMP binds to regulatory subunit on cAMP-dependent protein kinase to activate it . Kinase phosphorylates many proteins to amplify biological response .cAMP metabolized by phosphodiesterase (PDE) that concerts it to inactive metabolite (5’AMP subunit of protein kinase)

Question 39

Cyclic GMP pathway

Answer 39

. Generated by guanylyl cyclase . Main target is cGMP-dependent protein kinase (PKG) .cGMP directly activates several ion channels or ion pumps that participate in modulating cytoplasmic Ca levels in smooth muscle and sensory tissue . Activation of ion channels directly by cGMP binding to from phosphorylation by PKG that alters cytoplasmic Ca . Production regulated by activation of cytoplasmic or membrane localized form of GC

Question 40

GCs

Answer 40

. Targets of NO produced by endothelial cells | . Pathway mediates smooth muscle relaxation and neurotransmission

Question 41

IP3 and DAG pathway

Answer 41

. Gq activates membrane bound phospholipase C . Catalyze breakdown of membrane PIP2 to DAG and IP3 . DAG activates PKC that phosphorylates proteins . IP3 binds to IP3 receptor (ligand-gated ion channel) in ER to induce Ca release . Result is inc. intracellular Ca

Question 42

How Ca induces cellular responses

Answer 42

. Binding to calmodulin . Combining to other Ca-binding proteins . Directly binding to and affecting target proteins

Question 43

Ways to inc. intracellular Ca

Answer 43

. Directly through Ca channels in surface membrane | . Release from intracellular Ca stores

Question 44

Main intracellular Ca store is ___

Answer 44

. In the ER

Question 45

Ca release from ER

Answer 45

. Through ryanodine and IP3 ligand-gated receptors . Ryanodine: more specialized, involved in excitation-contraction coupling in muscle and Ca induced Ca release in neurons . IP3R: more ubiquitous role, present in all types of cells

Question 46

AChE inhibitors

Answer 46

. Used for glaucoma, inc. GI motility, and myasthenia Gravis

Question 47

Disposition of NE neurotransmitter

Answer 47

. Presynaptic: uptake by active pump uptake-1 (inhibited by cocaine and tricyclic antidepressants), after uptakes by presynaptic neuron, NE metabolized by MAO enzyme . Target cells: uptake-2 pump (not cocaine sensitive), after uptake in postsynaptic cell, NE metabolized by COMT . Diffusion: detectable in plasma