The Peripheral Nervous System: Efferent Division Notes

The PNS serves as a crucial link between the Central Nervous System (CNS) and effector organs such as muscles and glands.
Much of the efferent output from the PNS is responsible for maintaining homeostasis within the body.
The PNS is divided into two main divisions:
- Autonomic Nervous System (ANS)
- It is the involuntary branch of the PNS.
- Innervates cardiac muscle, smooth muscle, most exocrine glands (such as sweat glands), certain endocrine glands, and adipose (fat) tissue.
- Somatic Nervous System
- It is responsible for voluntary control.
- Primarily innervates skeletal muscle.

The ANS utilizes an autonomic nerve pathway that extends from the CNS to the effector organ.
The functioning of the ANS is primarily controlled by two neurotransmitters:
- Acetylcholine (ACh)
- Epinephrine/Norepinephrine (Epi, NE)

The ANS features a two-neuron chain:
1. Preganglionic Neuron/Fiber:
- Extends from the CNS to the cell body of the second (postganglionic) neuron.
1. Postganglionic Neuron/Fiber:
- Connects from the preganglionic terminal to the effector organ.

Most visceral organs are innervated by both sympathetic and parasympathetic neurons.
Generally, these divisions produce opposite effects in a given organ, allowing precise control over organ activity that maintains homeostasis:
- Sympathetic Nervous System:
- Dominant in emergency or stressful situations (often referred to as "fight, flight, fright").
- Prepares the body for strenuous physical activity.
- Parasympathetic Nervous System:
- Dominant during quiet, relaxed situations (often referred to as "rest & digest").
- Promotes body maintenance processes such as digestion.

The adrenal medulla is a component of the sympathetic nervous system.
It comprises chromaffin cells, which are modified sympathetic postganglionic cells that lack axons.
When stimulated, chromaffin cells secrete Epi and NE into the bloodstream as hormones.

Cells innervated by the ANS have distinct receptor types which determine their response to neurotransmitters:

Bind Acetylcholine (ACh):
- Nicotinic (Nic) Receptors:
- Bind ACh from preganglionic autonomic neurons of both the sympathetic and parasympathetic pathways.
- Muscarinic (Musc) Receptors:
- Bind ACh released from parasympathetic postganglionic neurons on effector cell membranes.

Bind Epinephrine and Norepinephrine:
- Alpha (α) Receptors:
- α1 Receptors:
  - Produce an excitatory response in most arterioles, leading to the contraction of smooth muscle.
- Beta (β) Receptors:
- β1 Receptors:
  - Lead to an excitatory response in the heart, increasing both heart rate and force of contraction.
- β2 Receptors:
  - Induce an inhibitory response in both arterioles and lung airways, resulting in relaxation of smooth muscle.

Sympathetic NS:
- Nicotinic receptors (Nic) respond to ACh.
- Alpha (α) receptors respond to Epi/NE:
- α1: Smooth muscle contraction.
- Beta (β) receptors respond to Epi/NE:
- β1: Cardiac muscle stimulation.
- β2: Smooth muscle relaxation.

Comprises the axon of motor neurons originating from the ventral horn of the spinal cord.
These motor neurons innervate skeletal muscle and have cell bodies located within the CNS.
The axon of the motor neuron is a continuous pathway from its origin to the effector organ (skeletal muscle).
Upon stimulation, motor neurons release ACh at the neuromuscular junction (NMJ) and bind to nicotinic ACh receptors on the muscle, resulting in muscle contraction.

The NMJ is a synapse between a somatic motor neuron and a single muscle fiber (cell).
The cleft at the NMJ is too large for electrical transmission; thus, it relies on the chemical transmission of ACh.
When an action potential (AP) reaches the axon terminal, voltage-gated calcium channels open.
Calcium entry into the terminal leads to the release of ACh into the NMJ.
ACh binds to nicotinic ACh receptors on the motor end plate, causing Na+ channels to open, which leads to depolarization.
This results in an End-Plate Potential (EPP), a postsynaptic potential change caused by the influx of Na+.
If the potential reaches threshold, an AP is generated and propagated throughout the muscle fiber.

The AP reaches the axon terminal of the motor neuron.
Voltage-gated Ca2+ channels open, allowing Ca2+ into the terminal.
ACh is released into the NMJ.
ACh binds to postsynaptic receptors on the muscle fiber.
Non-specific cation channels open, causing an influx of Na+.
The EPP spreads across the motor end plate.
If the EPP reaches the threshold, voltage-gated Na+ channels open along the fiber membrane.
The action potential propagates along the muscle cell membrane.
ACh removal from the NMJ occurs to terminate signaling.

The motor end plate itself does not have a threshold, meaning it cannot independently initiate action potentials.
NMJ sites are located centrally along the cylindrical muscle fiber, and local current flow from the EPP spreads bidirectionally.
This spreading current reduces the membrane potential to threshold in adjacent areas, facilitating an action potential propagation away from the motor end plate.

Botulinum toxin type A inhibits the release of ACh at the NMJ.
It enters the neuron via endocytosis and disrupts vesicle binding to the membrane.
This is one of the most commonly performed cosmetic procedures in the United States, with 4.6 million total cases reported.

The black mamba is the fourth most venomous snake globally; it is highly aggressive.
Its venom poses a quadruple threat of dendrotoxins that act in succession:
1. Presynaptic Neurotoxins:
- Block voltage-gated K+ channels on motor neurons, preventing membrane repolarization.

An excess of ACh in the NMJ leads to muscle hyperexcitability and convulsive activity.
Postsynaptic Neurotoxins:
- Are nicotinic ACh receptor antagonists that bind irreversibly, preventing muscle depolarization.
  - Fatalities occur via respiratory paralysis as a consequence of the venom's action.