Autonomic Nervous System

Differences between Somatic Nervous System (SNS) and Autonomic Nervous System (ANS)

 

Table 1: Provide the major differences available between SNS and ANS 
 
The fig.1 provide the basic information about the arrangements of neurons with respect to the tissues in SNS and ANS
 
 
Fig. 1 Representation of Somatic motor nerve and the efferent nerve of the ANS.The principle neurotransmitters, acetylcholine (ACh) and norepinephrine (NE) are shown in red.The receptor for these neurotransmitters, nicotinic (N) and muscarinic( M) cholinergic receptors, α and β adrenergic receptors are shown in green.The somatic nerve directly innervate the skeletal muscle (without any ganglionic relay).The autonomic efferent nerves innervated secretory glands, smooth muscle, and cardiac tissue. Both parasympathetic and sympathetic divisions have ganglia where ACh is the neurotransmitter of pre-ganglionic neurons.ACh acts on nicotinic receptors on post-ganglionic neurons.ACh is also the neurotransmitter at the adrenal medulla cells and acts via nicotinic receptors to cause the release of epinephrine (EPI) and NE.ACh is also the neurotransmitter of post-ganglionic parasympathetic neurons and acts on muscarinic receptors. NE is the principal neurotransmitter of post-ganglionic sympathetic neurons and works via α and β adrenergic receptors.The somatic nerve forms a specialized synaptic junction with a skeletal muscle called the motor end plate.The ganglia in the parasympathetic division are near to or within the innervated organ with one on one relationship between the pre-ganglionic and post-ganglionic neurons.In sympathetic division, the ganglia are generally far from the effector cells. A pre-ganglionic neuron may make contact with a large number of post-ganglionic neurons.


Cholinergic transmission


The synthesis, storage, and release of ACh follow a similar life cycle in all cholinergic synapses i.e.,
        Skeletal neuromuscular junctions (motor end plate)
        Pre-ganglionic sympathetic and parasympathetic terminals
        Post-ganglionic parasympathetic varicosities

Two enzymes, choline acetyltransferase(ChAT) and acetylcholinesterase (AChE) are involved in ACh synthesis and hydrolysis, respectively.

ChAT catalyzes the acetylation of choline with acetyl coenzyme A (CoA).

Following the synthesis of ACh in the cytoplasm of cholinergic neurons, ACh is transported into synaptic vesicles by vesicular ACh transporter (VAChT) via a proton electrochemical gradient.

Upon depolarization of the nerve terminal, the release of ACh occurs via exocytosis. Depolarization allows the entry of Ca2+ into the cytoplasm which promotes the fusion of the vesicular membrane with the plasma membrane for exocytosis to occur.

Once ACh is released from the cholinergic neurons, ACh is hydrolyzed by AChE to acetate and choline.

The availability of choline is crucial for the synthesis of ACh and choline is provided from the diet.

Choline is taken up from the extracellular space by two transport systems
        a.     Na+ independent transport system
        b.     Na+ and Cl- dependent choline transport system (responsible for                        providing choline for ACh synthesis in neurons)

Choline is recycled after re-uptake into the nerve terminal of cholinergic cells and reused for ACh synthesis.

Cholinergic receptors and signal transduction


There are two broad categorize of the cholinergic receptors
        a. Nicotinic receptor (N)
        b. Muscarinic receptor (M)

Nicotinic receptor (N)

The action of ACh specific to nicotinic receptors can be obtained by using nicotine alkaloid
The nicotinic receptors are ligand-gated ion channels.
Nicotinic receptors are further subdivided as

            1. Muscle type (Nm)                         

                    Found in vertebrate skeletal muscles

            2. Neuronal type (Nn)

                    Found in autonomic ganglia  the CNS and in non-neuronal tissues

Muscarinic receptor (M)

Muscarinic receptors can interact with muscarine alkaloid and responses similar to ACh can be obtained by muscarine in these receptors
Muscarinic receptors are G protein coupled receptors (GPCRs).
Muscarinic receptors are further subdivided as 

        1. M1

        2. M2

        3. M3

        4. M4

        5. M5 

 
The M1, M3, and M5 sub-types works through the activation of phospholipase C (PLC) via Gq/11. This results in the hydrolysis of membrane phosphatidylinositol 4,5 diphophate (PIP2) to form Inositol triphosphate(IP3) and Diacylglycerol (DAG).
IP3 causes release of intracellular Ca2+  and results in contraction and secretion from glands.
Whereas, DAG activates Protein kinase C (PKC) which leads to the phosphorylation of various proteins and results in various physiological responses.

The M2 and M4 receptos interact with other G proteins (Gi and Go) that causes inhibition of adenylyl cyclase(AC) and resulting in the decrease of cyclic AMP (cAMP), activation of inwardly rectifying K+ channel, and inhibition of volatage-gated Ca2+ channel.
The physiological effects are hyperpolarisation and inhibition of membrane excitation.
 
Table 2: Different receptors of cholinnergic system

Adrenergic Transmission


Under this category, following are the neurotransmitters.
    Norepinephrine (NE) in most sympathetic post-ganglionic neurons
    Dopamine (DA) in mammalian extrapyramidal system, several mesocortical        and mesolimbic neuronal pathyways
    Epinephrine, major hormone of adrenal medulla
Collectivey, NE, DA and epinephrine are known as catecholamines
Catecholamines are stored in vesicles and opening of voltage-gated Ca2+ channels results in the release of these catecholamines in the synaptic cleft.
 
Synthesis of catecholamines
 The interaction of NE and epinephrine with their receptors is terminated by
        a. reuptake of NE and epinephrine into nerve terminal by NE tranporter                (NET) or uptake 1
        b. dilution by diffusion out of the synaptic cleft and uptake by extaneural                sites by extraneuronal transporter (ENT) or uptake 2, organic                    cation transporter 1 (OCT1) and organic cation transporter 2                    (OCT2)

After uptake, catecholamines can be metabolised or restored. Two enyzmes are significant in the initial metabolic transformation of catecholamines i.e., 
        a. monoamine oxidase (MAO)
        b. catechol-O-methyltransferase (COMT)

Adrenergic receptors and signal transduction

The adrenergic receptors are divided as 

α adrenergic receptor

        1. α1 Post-synaptic receptor

        2. α2 Pre-synaptic receptor (have an inhibitory effect on NE release)

β adrenergic receptor

        1. β1 adrenergic receptor (cardiac muscle)

        2. β2 adrenergic receptor (smooth muscle)

        3. β3 adrenergic receptor (adipose tissue)

All the adrenergic receptors are GPCRs

Table 3: Different receptors of adrenergic system

Acknowlegment: All the images were prepared in www.biorender.com

Reference: 

Brunton, Laurence, B. A. Chabner, and B. C. Knollmann. "Goodman and Gilman’s the pharmacological basis of therapeutics. Twelfth." (2011): 1808.

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