1. ANS Review

2. ANS maintains you & allows you to respond to the environment
SYMPATHETIC
Mobilizes body to expend energy
Targets widely distributed organ systems
Blood vessels, sweat glands,
piloerector muscles

3. FEAR

4. Sympathetic & adrenal medulla: Fight or flight response
mobilizes the body to expend energy for extreme sustained physical exertion .
Cardiovascular System
Increase in heart rate & force of contraction  increased cardiac output (5L/min  25-40L/min)
Increase in BP
Redistribution of blood flow
Respiratory System
Airways are dilated
Digestive System
GI function (motility and secretions) inhibited
Metabolism
Glucose is mobilized
Lipolysis is stimulated
Metabolic rate increases

5. Stimuli that release adrenal medullary catecholamines
Physiological stressors
Psychological: emotional states - fear
Metabolic
Hypothermia
Pathological stressors
Severe hemorrhage
Heart attack
Pain
NOTE: Asthmatic attacks do not release CAs

6. ANS maintains you & allows you to respond to the environment
SYMPATHETIC
Mobilizes body to expend energy
Targets widely distributed organ systems
PARASYMPATHETIC
Restorative role; conserves energy
Discrete targeted control

7. General feature of ANS Tonically active system
Always have basal level of end organ activity
Often modulates ongoing spontaneously generated activity (heart; GI tract)
Activity controlled reflexly & most autonomic reflexes are readily affected by emotional state

8. Schematic ANS: Organization
post
pre
Parasympathetic
Cranial
Spinal cord
pre T1
post
Sympathetic
Thoraco-lumbar
pre
Collateral ganglia
Adrenal
Splanchnic nerve L3
Parasympathetic
post
pre
Sacral S2 S3 S4
Schematic ANS: Organization

9. Schematic ANS: Wiring of ganglia
1:1/1:2
pre
Targeted control
Parasympathetic
Cranial
Spinal cord
Diffuse targets
Divergence/convergence T1
Sympathetic
pre
Collateral ganglia
Adrenal
Splanchnic nerve L3
Parasympathetic
1:1/1:2
pre
Sacral S2 S3 S4
Targeted control
Schematic ANS: Wiring of ganglia

10. Neuroeffector junction: Sympathetic postganglionic nerve terminal is a diffusely distributed complex branching network with varicosities (swellings)
Synaptic vesicle

11. ANS TRANSMITTERS Ach Ach Ach Ach Ach Ach Ach
Spinal cord
Sympathetic postganglionics
to sweat glands
Ach
Ach T1
Ach
Biological inactivation:
Breakdown: acetylcholinesterase
Resupply: De novo synthesis in terminal
Adrenal L3
Ach
Ach S2 S3 S4
All preganglionic neurons release Ach
All postganglionic parasympathetic neurons
release Ach
Sympathetic postganglionics  general sweat glands (except sweat gland on palms, soles of feet, & underarms) release Ach

12. ANS TRANSMITTERS Ach Ach Ach NE Ach NE EPI – 80% Ach Ach
Spinal cord
Ach T1 NE
Ach NE
EPI – 80%
Biological inactivation of NE:
REUPTAKE
Resupply of NE: recycling &
new synthesis
Adrenal L3
Ach
Ach S2 S3 S4
Sympathetic postganglionic neurons release NE (except to generalized sweat glands; Adrenal medulla releases NE and EPI (80%)
Peptides also in LDCV in terminals along with Ach & NE

13. Peptides Stored in LDCV Never located at plasma membrane
Released only by high frequency stimulation
Peptides augment actions of low molecular weight transmitter (ACh or NE)
Biological inactivation: breakdown by peptidases

14. ANS RECEPTORS – ganglion - nicotinic
Ach
Ach
nicotinic
Spinal cord
nicotinic
Ach T1 NE
Ach
Differences between ganglionic
& skeletal NMJ nicotinic receptors:
Subunit composition
Sensitivity to antagonists
nicotinic L3
Ach
Ach S2 S3 S4
nicotinic
Somatic motor nerve
Skeletal NMJ
All postganglionic neurons, cells of the adrenal medulla & skeletal NMJ have nicotinic cholinergic receptors

15. ANS RECEPTORS (+) (-) (+) Ach Ach Spinal cord muscarinic Sweat gl. (+)
Sympathetic postganglionics to generalized sweat glands release Ach
(+)
Ach T1
Ach
muscarinic L3
Ach
Ach
(+) S2 S3 S4
Cholinergic receptors of the muscarinic type are on effector tissues innervated by parasympathetic postganglionic neurons and on generalized sweat glands

16. Schematic ANS ANS RECEPTORS -Adrenergic NE EPI NE Alpha-1 & 2
post
pre
Parasympathetic
Cranial
Spinal cord NE
pre T1
post
Sympathetic
pre
EPI NE
Alpha-1 & 2
Beta-1 & 2
Adrenal
Splanchnic nerve L3
Parasympathetic
post
pre
Sacral S2 S3 S4
Schematic ANS

17. Receptors for NE Alpha-1 receptors
Excitatory  contraction of smooth muscle
Most important location -- smooth muscle of blood vessels
Insensitive - require high concentrations of agonist; NE & EPI ~ equipotent
Under physiological conditions, a-1 receptors are activated by NE released from sympathetic nerves.
EPI released from adrenal in response to stress never reaches high enough concentrations in the circulation to activate a-1 receptors
Effects mediated by IP3 production

18. Receptors for NE Alpha-2 receptors are presynaptic
Inhibitory receptors located on nerve terminals.
Autoreceptors on sympathetic postganglionic terminals;
Hetero-receptors on terminals of parasympathetic nerves of the GI tract bind NE, released from adjacent postganglionic sympathetic nerves.
Activation of a-2 receptor reduces evoked transmitter release by reducing Ca2+ entry into presynaptic terminal
a-2 heteroreceptors mediate sympathetic inhibition of GI tract

19. BETA-1 RECEPTORS Excitatory response to both NE & EPI
Location – heart: beats faster and more strongly
Beta-1 receptor is very sensitive to both NE & EPI – so heart can be stimulated by NE released from sympathetic nerves or EPI released from the adrenal medulla
Beta-1 effects mediated by stimulation of cAMP production

20. BETA-2 RECEPTORS inhibitory  relaxation of smooth muscle
very sensitive to EPI, but not NE
activated in response to stress (when adrenal medulla secretes EPI into the circulation)
found on smooth muscle of airways, GI tract, & blood vessels supplying skeletal muscle (along with alpha-1 receptors)
Beta-2 agonists used for acute treatment of asthmatic attacks
stimulate production of cAMP

21. Blood vessels of skeletal muscle

22. Transmitter
Receptor
Action
Target
Signalling Mechanism
ACh
nicotinic
+++
Postganglionic neurons
Ligand gated ion channel
depolarization
muscarinic
---
Smooth m
Glands
Heart
GPCR
IP3 induced Ca release
Opens K+ channel NE
a-1
a-2
----
Nerve varicosities
IP3 induced
Ca release
Ca entry
EPI
b-1
cAMP
b-2

24. Examples of ANS Reflexes
Pupillary light reflex
Stress activation of the adrenal medulla
Reflex regulation of the GI tract (CNS & LOCAL)
Parasympathetic Nervous System
Vago-vagal activation of stomach (CNS)
Gastro-colic reflex (CNS)
Enteric Nervous System - Locally mediated stereotyped movements (e.g. peristalsis)
Sympathetic Nervous System
Global inhibition (stress response - CNS)
Enterogastric reflex: selective local inhibition:
Tonic inhibition (local)

25. ENS
PARASYMPATHETIC
SYMPATHETIC