Autonomic Nervous System PDF

**The Autonomic Nervous System (ANS)** The ANS is part of the **peripheral nervous system (PNS)** and includes: - **Sympathetic Division (SNS):** Prepares the body for \"fight or flight\" responses. - **Parasympathetic Division (PNS):** Manages \"rest and digest\" activities. The ANS...

**The Autonomic Nervous System (ANS)** The ANS is part of the **peripheral nervous system (PNS)** and includes: - **Sympathetic Division (SNS):** Prepares the body for \"fight or flight\" responses. - **Parasympathetic Division (PNS):** Manages \"rest and digest\" activities. The ANS works automatically (without conscious effort) and coordinates with the endocrine system to maintain homeostasis. - **Parabrachial nuclei** (behavioral response to taste- hence role in conditioning) - **reticular formation** - **Hypothalamus** - **PAG\*\*→ medullary** - **Amygdala** **Organization of the ANS** The ANS operates through two main neuron chains: 1. **Preganglionic Neurons** (from the CNS to a ganglion). 2. **Postganglionic Neurons** (from the ganglion to the target organ). These neurons control organ functions based on inputs from the brain, spinal cord, and sensory information. **Sympathetic Division (SNS)** - **Preganglionic neurons:** Originate in the spinal cord **(T1-L3)** and travel to the sympathetic ganglia. - **-** **Preganglionic fibers emerge as spinal nerves T1 -- L3. and project via white rami (type B, myelinated) to the paravertebral ganglia/ sympathetic chain (bilateral). At this junction/synapse → NT is ACh.** - **-** **Exceptions:** - **Postganglionic fibers (type C) -- projects to effectors (long)** - **Other ganglia in sympathetic chain** - **Postganglionic neurons:** Send signals to organs and tissues, often causing a widespread response. - **Neurotransmitters:** Norepinephrine (NE) is the primary transmitter in postganglionic fibers, targeting **adrenergic receptors** (α and β) on tissues. - **Adrenal Medulla:** Functions like a postganglionic neuron, releasing NE and epinephrine into the bloodstream for a powerful, sustained response. **Parasympathetic Division** - Nuclei located at 2 points : 1\) **Brain stem** where there are **4 nuclei viz:** i. **Edinger-Westphal,** ii. **Salivatory(superior),** iii. **Salivatory(inferior) &** iv. **Dorsal motor nucleus of vagus nerve** v. **Motor output of these nuclei via cranial nerves 3,4,7,9,10** 2**) Sacral area** (lateral gray matter) Output via spinal nerves **S2-S4** hence craniosacral outflow - **Preganglionic neurons:** Start in the brainstem or sacral spinal cord and travel to ganglia near or within the target organs. - **Postganglionic neurons:** Shorter, directly innervating target organs for more specific responses. - **Neurotransmitters:** Acetylcholine (ACh) is used by both pre- and postganglionic neurons, acting on **cholinergic receptors** (muscarinic and nicotinic). - **Changes in receptor density alters sensitivity** **ANS Action** - **Balance of SNS and PNS:** At rest, both divisions are active, maintaining a \"tone\" that can shift depending on the body\'s needs. - Other important characteristics: - **1) Responses often occur in anticipation of a disturbance**. - **2) Activity of ANS linked to activity of somatic NS** - Eg. **regulation of BP from supine to standing upright rapidly (orthostatic hypotension)** - Dysautonomia - **Sympathetic activation:** Increases heart rate, blood pressure, and prepares the body for physical activity. - **Parasympathetic activation:** Lowers heart rate, enhances digestion, and supports energy storage. **Receptors and Signal Transduction in the ANS** - **Cholinergic Receptors:** Respond to ACh, divided into: - **Nicotinic receptors (N1, N2):** Found in ganglia, **initiating rapid responses.** - Nicotinic receptors are activated by the binding of acetylcholine (ACh), a neurotransmitter released by nerve terminals. - Upon binding of ACh, the receptor undergoes a conformational change, opening its ion channel pore. - This allows the influx of sodium (Na+) and calcium (Ca2+) ions into the cell, leading to depolarization of the cell membrane. - Depolarization triggers an action potential, which propagates along the nerve or muscle fiber. - **Muscarinic receptors (M1-M5):** Located on target organs, **mediating slower, complex responses.** **Activation of Phospholipase C:** The activated G protein stimulates **the enzyme phospholipase C (PLC).** **Production of Second Messengers:** PLC **cleaves phosphatidylinositol 4,5-bisphosphate (PIP2)** into two second messengers: - **Inositol trisphosphate (IP3)** - **Diacylglycerol (DAG)** **Cellular Responses:** - IP3 binds to receptors on the **endoplasmic reticulum**, **causing the release of calcium ions (Ca2+) into the cytosol.** Increased intracellular Ca2+ can lead to various cellular responses, such as muscle contraction, secretion, and changes in gene expression. - **DAG activates protein kinase C (PKC),** which phosphorylates various proteins, leading to a wide range of cellular responses - **Adrenergic Receptors:** Respond to NE and epinephrine, classified as: - **Alpha receptors (α1, α2):** Regulate functions like blood vessel constriction. - **Beta receptors (β1, β2, β3):** Involved in heart rate modulation, airway dilation, and energy mobilization. - α1-adrenergic receptors are GPCRs, meaning they have **seven transmembrane domains.** - They are named after their affinity for the neurotransmitter norepinephrine (NE), also known as noradrenaline. - α1-adrenergic receptors are activated by the binding of NE, which is released by sympathetic nerve terminals. - Upon binding of NE, the receptor undergoes a conformational change, which activates the associated Gq protein. - The activated Gq protein then initiates a signaling cascade that leads to various cellular responses. 1. **Activation of Phospholipase C**: The activated Gq protein stimulates the enzyme phospholipase C (PLC). 2. **Production of Second Messengers**: PLC cleaves phosphatidylinositol 4,5-bisphosphate (PIP2) into two second messengers: - Inositol trisphosphate (IP3) - Diacylglycerol (DAG) 3. **Cellular Responses:** - IP3 binds to receptors on the endoplasmic reticulum, causing the release of calcium ions (Ca2+) into the cytosol. Increased intracellular Ca2+ can lead to various cellular responses, such as muscle contraction, secretion, and changes in gene expression. - **DAG activates protein kinase C (PKC**), which phosphorylates various proteins, leading to a wide range of cellular responses. - α1-adrenergic receptors are found in various tissues throughout the body, including smooth muscle, heart muscle, and liver cells. - They play a role in a variety of physiological functions, including vasoconstriction, increased heart rate, and glucose release from the liver. - α1-adrenergic receptor antagonists, such as prazosin, are used to block the effects of NE on α1-adrenergic receptors and are used in the treatment of hypertension and other cardiovascular disorders. **Inhibition of Adenylyl Cyclase**: The activated Gi/Go protein inhibits the enzyme adenylyl cyclase. **Reduction of cAMP Levels**: Adenylyl cyclase is responsible for converting ATP into cyclic AMP (cAMP). Therefore, inhibition of adenylyl cyclase leads to a decrease in cAMP levels. **Reduction of cAMP-dependent Protein Kinase Activity:** cAMP acts as a second messenger to activate cAMP-dependent protein kinase (PKA). Reduced cAMP levels lead to decreased PKA activity. **Cellular Responses**: The specific cellular responses triggered by decreased PKA activity will vary depending on the cell type and the downstream targets of PKA. However, common effects include **reduced cell proliferation, decreased secretion, and changes in ion channel activity**. **β1-adrenergic receptor** **Activation of Adenylyl Cyclase**: The activated Gs protein stimulates the enzyme adenylyl cyclase. **Production of cAMP**: Adenylyl cyclase converts ATP into cyclic AMP (cAMP). **Activation of Protein Kinase A (PKA)**: cAMP binds to and activates PKA. **Cellular Responses**: Activated PKA phosphorylates various proteins within the cardiac muscle cell, leading to a number of effects: - Increased Ca2+ influx through L-type calcium channels - Increased release of Ca2+ from the sarcoplasmic reticulum - Phosphorylation of contractile proteins, leading to increased contractility - Phosphorylation of the β1-adrenergic receptor itself, leading to desensitization **β2-adrenergic receptor** **Activation of Adenylyl Cyclase**: The activated Gs protein stimulates the enzyme adenylyl cyclase. **Production of cAMP**: Adenylyl cyclase converts ATP into cyclic AMP (cAMP). **Activation of Protein Kinase A (PKA):** cAMP binds to and activates PKA. **Cellular Responses**: Activated PKA phosphorylates various proteins within the smooth muscle cell, leading to a number of effects: - Decreased Ca2+ influx through L-type calcium channels in the cell membrane - Increased Ca2+ uptake into the sarcoplasmic reticulum - Decreased actin-myosin interactions, leading to muscle relaxation