Physio Autonomic NS (6)

• an involuntary system that regulates all the “vegetative” functions of the body
• has afferent input from Visceral afferents (eg. arterial BP, visceral pain), Somatic afferents (eg. surface pressure & pain), and Special senses (eg. visual, auditory)

• 1. parasympathetic
• 2. sympathetic
• 3. enteric

• unconscious or automatic responses that occur in specific patterns in response to specified sensory signals
• such reflexes can be demonstrated at the level of the spine, medulla oblongata, hypothalamus, & high centers like the thalamus or cortex

sweating & changes in cardiac & vascular function in response to pain or temperature stimulation

• where integration for blood pressure control occurs
• sensory input comes from stretch receptors (baroreceptors) in the walls of the aorta & carotid arteries

• the principal center for integration of the entire ANS
• contains nuclei integrating parasympathetic & sympathetic function

• serve as a place to integrate special sensory input
• eg. thalamus and cortex
• PNS & SNS signal integration is mediated by CNS

• Stress
• Anxiety
• Physical Activity
• Fear

• Sedentary Activity - things that happen when we're at rest
• Digestion/Eating
• “Vegging”

when output INCREASES in one division, it DECREASES in the other (don't get both types of stimulation to one organ at the same time)

• a neuron with a cell body located in the CNS innervates skeletal muscle
• upon activation neurons release ACh which act on nicotinic (N1) receptors on skeletal muscle cells at the NMJ

• has a cell body in the CNS, whose axon exits with a cranial or sacral nerve
• said neurons' axons exit the spinal chord & near to the effector organ in question, synapse w/ a postganglionic neuron in a parasympathetic ganglion
• preganglionic >> postganglionic (length-wise)

consist of short axons that innervate target organ cells

• long pre-ganglionic nerves originate in the CNS & synapse with short post-ganglionic nerves close to effector organs (smooth/cardiac muscle or glands)
• ACh is released at both ganglionic & effector organ synapses
• PNS ganglionic receptors: nicotinic (N2)
• effector organ receptors: muscarinic*

• NT = acetylcholine (ACh)
• receptor = nicotinic

acetycholine activates muscarinic receptors on cardiac muscle, smooth muscle, & glands

• has its cell body in Interomediolateral columns of the spinal cord at levels C8 → L3
• its axon exit in the anterior (ventral) nerve roots & synapse with post-ganglionic neurons in the sympathetic ganglia of
• 1. the sympathetic chain
• 2. collateral ganglia (eg. celiac ganglion)
• 3. terminal ganglia (near target organs, eg. bladder)

• has its cell body in a Paravertebral sympathetic chain ganglia or Collateral ganglia
• has a long axon that extends to target tissues

• short pre-ganglionic nerves originate in the CNS & synapse near the spinal chord w/ long post-ganglionic nerves
• ACh is released at all ganglionic synapses of the SNS
• NE is released at target organ synapses of the SNS

• NT = acetylcholine (ACh)
• receptor = nicotinic (N2)

• 1. norepinephrine → α or β receptors on cardiac muscle, smooth muscle, & glands
• receptors are coupled to G-proteins; function via a 2nd messenger system
• *NE is the main NT that innervates effector organs

• directly - there is no intermediate ganglion (sort of acts like a POST-ganglionic fiber)
• ACh acts on nicotinic (N2) receptors on the adrenal medulla
• the adrenal medulla in turn releases norepinephrine or epinephrine into circulation

• a paired bundle of nerve fibers that run from the base of the skull to the coccyx
• where many of the ganglion of the the SNS are located
• it can be found just outside the spinal chord

• nerves that travel down the spinal chord but bypass the sympathetic chain & synapse with ganglia outside of it (farther away from the spinal chord)
• includes celiac, superior, & inferior mesenteric ganglia

• cranial and sacral parts of the CNS (spinal chord)
• why it's called cranio-sacral

• sympathetic output is thoraco-lumbar (T1 → L3/4)
• while they originate in this middle-spinal region, SNS nerve axons can spread out through the spinal chord to reach all visceral organs of the body

• upon ACh stimulation, the PNS muscarinic receptors interact w/ heterotrimeric G-PROTEINS to bring about 1 of 3 responses:
• 1. hydrolysis of phosphoinositide → increasing Ca²⁺ → activating protein kinase C
• 2. inhibition of adenylyl cyclase → decreasing cAMP levels
• 3. modulating K+ channels (via G-Protein βγ complex)

b/c muscarinic responses are mediated by second messenger systems, in contrast with nicotinic responses, they tend to be SLOW & prolonged

• nicotinic receptor agonized by
• 1. ACh
• 2. decamethonium

• & antagonized by
• 1. D-tubocurarine
• 2. α-Bungarotoxin

is located on muscle cells at the NMJ; functions in the somatic motor system

are directly coupled to ion channels; DON'T function via 2nd messenger

• nicotinic receptor agonized by
• 1. ACh
• 2. Tetramethylammonium

• & antagonized by
• 1. hexamethonium

are located in ANS ganglia (SNS & PNS) & on adrenal medulla cells

are directly coupled to ion channels; DON'T function via 2nd messenger

• are all stimulated by ACh & muscarine but blocked by atropine & pirenzepine
• functions by activating the 2nd messengers IP₃ & diacylglycerol

• are both stimulated by ACh & muscarine but blocked by atropine & M2 is blocked by methoctramine
• functions by decreasing the level of the 2nd messenger cAMP

• α₁ & α₂ preferentially bind to NE > EPI → agonism
• β₁, β₂, & β₃ preferentially bind to EPI > NE → agonism
• all work via 2nd messengers
• α₁: IP₃ & diacylglycerol
• α₂: ↓ cAMP
• β₁: ↑ cAMP
• β₂: ↑ cAMP
• β₃: ↑ cAMP

• found most abundantly in blood vessels (*especially arterioles)
• stimulation usually CONSTRICTS vessels via Ca²⁺ mobilization caused by 2nd messengers IP₃ & diacylglycerol
• α₁ activation results in elevated BP [b/c of BV constriction]

• located primarily on the surface of PRE-synaptic neurons in the brain
• when stimulated they SUPPRESS the release of norepinephrine from pre-synaptic terminals by inhibiting adenylate cyclase
• *are sometimes referred to as auto-inhibitory receptors
• [alpha-2 will auto-inhibit YOU]

• primarily located in the heart
• when stimulated they INCREASE heart rate & contractility by ↑ cAMP & activating adenylate cyclase

• located primarily in the lungs, specifically bronchial smooth muscle
• when stimulated they cause bronchodilation by ↑ cAMP & activating adenylate cyclase

located on adipose cells where they mediate lipolysis (the breakdown of lipids; involves hydrolysis of TAGs into glycerol & free FAs)

• 1. by having opposing smooth muscles innervated separately - 1 by the PNS, the other by the SNS (eg. iris)
• 2. by having the same cells innervated by both PNS & SNS neurons, expressing receptors for both ACh & NE (eg. heart's sino-atrial node (pacemaker))

• dilation occurs via sympathetic stimulation which contracts the Radial smooth muscle by activating α₁ receptors
• constriction occurs via parasympathetic stimulation which contracts the Sphincter smooth muscle by activating muscarinic receptors
• SNS activates the dilating muscle (radial, organized like spokes of a wheel)
• PNS activates the constricting muscle (sphincter, circular, runs around the iris)

• SNS stimulation of the Cardiac plexus speeds firing rate via β receptors
• PNS stimulation of the Vagus nerve SLOWS firing rate via muscarinic receptors
• heart has receptors for BOTH systems

• Tyrosine
• ↓ (+ OH)
• Dopa
• ↓ (- COOH)
• Dopamine (+ OH)
• ↓ (+ OH)
• NE
• ↓ (+CH₃ via phenylethanolamine-N-methyltransferase)
• EPI
• *in the final step epinephrine is made from norepinephrine by the action of N-methyl transferase, an enzyme only found in adrenal medullary cells

• steroids from the adrenal cortex delivered via a small portal system to the medulla
• means an increased synthesis of EPI from NE

• 1. although most receptors at ANS ganglia are N2 nicotinic, MUSCARINIC receptors may sometimes be found in ganglia (ACh can bind & activate both receptor types)
• 2. there are non-cholinergic, non-adrenergic transmitters in the ANS (co-transmission)

when at the ganglion it contains both N2 & Muscarinic receptors

N2 stimulation by ACh results in fast post-ganglionic EPSPs (b/c they directly control ion channels)

Muscarinic stimulation by ACh results in slow post-ganglionic EPSPs (b/c they are G-protein coupled)

this applies to both SNS & PNS ganglia

in many pre & post ganglionic neurons of the ANS, transmitters in addition to ACh & NE are expressed & participate in neurotransmission

• 1. mainly by re-uptake into adrenergic nerve terminals via active transport
• 2. the enzyme catechol-O-methyl transferase may inactivate NE (+ other catecholamines) by methylating an OH group; this enzyme is present NEAR the postsynaptic membranes of most target tissues
• 3. by MAO (monoamine oxidase) INSIDE the neuron

local anesthetics (+ cocaine) have been shown to inhibit the re-uptake, thereby increasing the concentration of NE available to target cell receptors