1b: Central regulation and signal transduction

Learning Outcomes

  • Contrast the afferent (sensory) and efferent (motor) branches of the somatic and autonomic nervous systems (voluntary/conscious control vs involuntary regulation of internal organs).

    • Understand Afferent:

    • Prefix "A" (Latin Ad) implies towards the CNS (central nervous system).

    • Understand Efferent:

    • Prefix "E" (Latin Ex) implies away from the CNS.

  • Discuss the relative contributions of the sympathetic and parasympathetic divisions of the autonomic nervous system in the regulation of physiology.

  • Appreciate the link between autonomic control centers in the brainstem and unconscious functions of the ANS.

  • Describe the parasympathetic functions of the vagus nerve.

  • Appreciate the range of sensory receptor types.

  • Explain why the sympathetic nervous system is commonly referred to as the “fight or flight” response while the parasympathetic nervous system is referred to as “rest and digest.”

  • Describe the role of the adrenal gland in sympathetic mass discharge.

  • Explain the concept of autonomic tone and the relative contribution of the two divisions of the autonomic nervous system in maintaining the basal activity of an organ at the resting state.

  • Appreciate the example of autonomic tone being the cardiovascular system.

  • Describe the major anatomical and physiological differences of the sympathetic and parasympathetic neurons.

  • Define adrenergic and cholinergic neurons.

  • Describe the three types of signal transducing membrane receptors and their mechanisms.

  • Define the role of second messengers in signal transduction and identify

    • The major components (enzymes and second messengers) within G protein signal transduction pathways involving:

    • Gs

    • Gi

    • Gq

  • Explain the concepts of amplification and termination in signal transduction.

Overview of the Nervous System

  • The nervous system comprises two major parts:

    • Central Nervous System (CNS)

    • Peripheral Nervous System (PNS)

  • The autonomic nervous system (ANS) can be divided into two branches:

    • Sympathetic Nervous System (SNS) - fight or flight, turbo

    • Parasympathetic Nervous System (PNS) - rest and digest, recharge

  • Note: The somatic nervous system and action potentials will be addressed in week 2.

Somatic vs. Autonomic Systems

Somatic Nervous System - conscious control, voluntary

  • Controls voluntary movements via conscious awareness.

  • Neurotransmitter: Acetylcholine

  • Effector organs: Skeletal muscle

Autonomic Nervous System - automatic regulation of internal organs, involuntary

  • Regulates involuntary functions and homeostasis.

  • Divided into sympathetic and parasympathetic divisions.

  • Neurotransmitters:

    • Sympathetic: Norepinephrine (NE)

    • Parasympathetic: Acetylcholine (ACh)

    • Includes the adrenal medulla, which releases epinephrine and norepinephrine.

    • Effector Organs: Smooth muscle, cardiac muscle, glands.

Autonomic Nervous System Functions

  • Evaluates the internal environment and maintains homeostasis.

  • Sensory neurons connect sensory receptors to the CNS (hypothalamus and medulla oblongata).

  • Motor neurons connect the CNS to effectors (organs or tissues).

  • Autonomic functions often operate as reflexes (e.g., enteric nervous system).

  • Significant role in cardiovascular and respiratory system functioning, important pharmacological targets.

Sensory Receptors

  • Different types of receptors exist, each responsible for detecting different environmental stimuli:

    • Mechanoreceptors (e.g., Pacinian corpuscle for touch)

    • Photoreceptors (e.g., rods and cones for vision)

    • Chemoreceptors (e.g., for taste and olfaction)

    • Thermoreceptors (e.g., for temperature)

    • Nociceptors (e.g., for pain)

  • Each receptor type has specific modalities, locations, and functions.

Autonomic Control Centers in the Brain Stem

  • Control centers in the brainstem regulate bodily functions governed by the ANS.

  • Structures Include:

    • Hypothalamus: regulates water balance, temperature, hunger, and eating behavior.

    • Pons: involved in respiration.

    • Medulla: regulates cardiac output, gastric function, and automatic reflexes like vomiting and swallowing.

  • Note: Focus on the concept of regulatory centers; specific functions of brain structures should not be memorized.

Divisions of the Autonomic Nervous System

  • Sympathetic Division: fight or flight

    • Increases alertness, energy, heart rate, blood pressure, and breathing rate.

    • Triggered by stressors like fear and pain.

  • Parasympathetic Division: rest and digest

    • Decreases alertness, heart rate, blood pressure, and aids in digestion and relaxation.

    • Heavily involved in the functions of the vagus nerve.

    • vagus nerve also helps with defection, urination, and sexual arousal

Opposing Effects of ANS Divisions

  • Physiological changes induced are opposite between the parasympathetic and sympathetic divisions.

  • Examples:

    • Parasympathetic: constricts pupils; stimulates salivation; slows heartbeat.

    • Sympathetic: dilates pupils; inhibits salivation; accelerates heartbeat.

Anatomical and Functional Differences of ANS Divisions

  1. Spinal cord exit site:

    • Sympathetic: thoracolumbar region.

      • sympathetic output can activate many organs at once

      • coordinated fight or flight response

    • Parasympathetic: craniosacral region.

      • parasympathetic fibres go directly to specific organs

  2. Neurotransmitters used in postganglionic fibers.

  3. Receptors expressed at target tissues.

  4. Activity of target tissues relates to specialized functions of target cells.

Ganglia and Neurons

sympathetic:

  • Preganglionic neurons originate within the CNS.

  • preganglionic fibres exit at the thoracic level

  • ganglia - little clusters of neuron cell bodies located outside of the CNS

    • acts as a ‘relay station’

  • sympathetic ganglia are found in paravertebral chains

  • ganglia far from organs

  • preganglionic length - short

  • postganglionic length - long

parasympathetic:

  • preganglionic fibres exit the CNS in the cranial and sacral levels

  • ganglia are located adjacent to or within the tissue wall of the target organ

  • post ganglionic length - short

  • pre ganglionic length - long

length: how far each axon has to travel

  • preganglionic neurons are within the CNS, their cell bodies are in the brainstem or spinal cord

  • postganglionic neurons, their cell bodies are outside the CNS, in the autonomic ganglia

types of neurotransmitter that postganglionic neuron releases:

  • adrenergic

    • when a neuron releases norepinephrine (NE)

    • most sympathetic postganglionic neurons

    • for fight or flight

  • cholinergic

    • when a neuron releases acetylcholine (ACh)

    • parasympathetic postganglionic neurons

    • for rest and digest

Mass Discharge and Sympathetic Activation

  • Definition: Coordinated discharge of sympathetic neurons in response to stress.

  • Known as the “fight or flight,” “alarm response,” or “stress response.”

  • triggered by fear and pain

  • hypothalamus activates sympathetic division of nervous system

  • heart rate, blood pressure, and respiration increase

  • adrenal medulla secrete epinephrine and norepinephrine

  • blood flow to skeletal msucles increases

  • stomach contractions are inhibited, contracts less

  • acute vs chronic activation (oral pres vs chased by bear)

homeostasis is a dynamic balance between autonomic branches

  • organ systems are balanced between the input from the sympathetic and parasympathetic divisions

  • when something upsets that balance, the homeostatic mechanisms strive to return it to its regular state

  • for each organ system, there may be more of a sympathetic or parasympathetic dominance to the resting state.

    • even when you’re not stressed and not actively digesting, one branch of the autonomic nervous system tends to be the ‘default controller’ for that organ

Autonomic Tone: single system

  • Refers to the baseline activity of both the sympathetic and parasympathetic systems.

  • Sympathetic activity regulates increases and decreases in organ activity.

  • Local sympathetic tone modulates blood flow, maintaining rest conditions at approximately 50% arterial diameter.

  • when sympathetic nervous system regulates both increases and decrease in activity of a stimulated organ

    • usually in the blood vessels

  • vascular tone: baseline level of contraction in your blood vessels

  • local cympathetic vascular tone regulates local blood flow into tissues

  • under resting conditions:

    • sympathetic NS maintains artery diameter at ~50% of maximum

  • increasing sympathetic stimulation

    • increasing sympathetic stimulation constricts the smooth muscles, increasing resistance in the arteries = increased blood pressure = decreased blood flow

    • decreasing sympathetic activity relaxes the muscle, decreasing resistance in the arteries = increased flow, decreased blood pressure

Signal Transduction

  • Three types of signal transducing membrane receptor proteins exist:

    1. Ion-Channel-linked

      • muscle related

    2. G-Protein-linked

      • regulates enzyme activity and are characterised by their self-limiting process via GTPase activity

    3. Enzyme-linked

      • related to growth factors

      • cytokines

G Proteins

  • Features of G proteins:

    • cell-surface receptors

    • GTP = high energy state

    • GDP = low energy state

    • the alpha subunit of the g protein can turn itself off by breaking down GTP to GDP

  • Gs - stimulatory

  • Gi - inhibitory

  • Gs + Gi regulates the activity of adenylyl cyclase and resulting formation of cyclic AMP (cAMP)

  • Gq coupled to phospholipase C and signal via inositol triphosphate (IP3) and release of intracellular calcium (Ca++)

    • Rapid amplification.

    • Rapid termination of enzyme activation.

    • GTPase activity leads to attenuation of secondary signals.

    • Various pathways regulated include:

    • Phosphodiesterase cleaving cAMP.

    • K+ flux restoration by Na+/K+ ATPase.

    • Ca2+ flux reverses from the ER/SR by Ca2+ ATPase.

    • Rapid degradation of IP3 by monophosphatases.

Signal Transduction Pathways

  • G subunit types define the pathways via which signals are transduced:

    • Gs and Gi regulate cyclic AMP production by adenylyl cyclase.

    • Gq couples with phospholipase C leading to inositol triphosphate (IP3) and intracellular calcium release.

Receptor Activity and Signaling Mechanisms

  • Ligand binding to GPCR activates G proteins and signal transduction pathways, including phospholipase C activation, leading to further signaling events.

  • Termination of signaling occurs via GTPase activity and hydrolysis of signaling molecules like IP3.

Conclusion

  • Understanding the complexity and interrelation between the sympathetic and parasympathetic divisions is crucial for grasping autonomic regulation in physiology.

  • The balance between these two systems is essential for maintaining homeostasis in various bodily functions.

Nature of the receptor on the target tissue

  • sympathetic = adrenergic receptors that signal via G protein complexes

    • alpha forms mostly activate Gq (cuts, calcium mobilising), Gi

    • beta forms mostly activate Gs

  • parasympathetic - cholinergic synapses

    • muscarinic receptors that mostly signal through Gi or Gq

    • Nicotinic receptors that activate gated ion channels