Ch 8B Neurons: Cell and Network Properties – Synaptic Communication and Neurocrines

Neurons: Cell and Network Properties

Introduction

This section explores the mechanisms by which neurons communicate within the nervous system, focusing on synaptic transmission, neurocrine signaling, and the classification of neurotransmitters and their receptors. Understanding these processes is fundamental to the study of human physiology and the function of neural networks.

Cell-to-Cell Communication: Synapses

Types of Synapses

• Electrical Synapses: Pass electrical signals directly through gap junctions between adjacent cells.

• Bi-directional Signaling: Electrical signals can travel in both directions, allowing rapid and synchronized activity across a network of cells.

• Chemical Synapses: Use neurotransmitters released into the synaptic cleft to transmit signals between neurons.

Neurotransmitters, Neuromodulators, and Neurohormones

• Neurotransmitters: Fast-acting chemical messengers that transmit signals across synapses.

• Neuromodulators: Slow-acting chemicals that modulate synaptic transmission and neuronal activity.

• Neurohormones: Chemicals released into the blood to act on distant targets.

Cell-to-Cell: Neurocrine Receptors

Types of Neurocrine Receptors

• Ionotropic Receptors (Receptor-Channels): Mediate rapid responses by directly altering ion flow across membranes.

• Metabotropic Receptors (G Protein–Coupled Receptors): Mediate slower responses, often by opening or closing ion channels indirectly through intracellular signaling pathways.

Agonists and Antagonists

• Agonists: Molecules that mimic the action of neurotransmitters by binding to and activating receptors.

• Antagonists: Molecules that inhibit neurotransmitter activity by binding to receptors and blocking activation.

Classification of Neurocrines

Seven Classes by Structure

• Acetylcholine

• Amines

• Amino acids

• Peptides

• Purines

• Gases

• Lipids

Receptors

Cholinergic Receptors

• Nicotinic Receptors: Found on skeletal muscle, autonomic division of the PNS, and CNS. These are monovalent cation channels permeable to Na+ and K+.

• Muscarinic Receptors: Located in the CNS and autonomic parasympathetic division of the PNS. These are G protein–coupled receptors.

Amines

Overview

• Active in the CNS

• Derived from single amino acids:

  • Tryptophan → Serotonin

  • Histidine → Histamine

  • Tyrosine → Dopamine, Norepinephrine, Epinephrine

Adrenergic Receptors

• Alpha (α) and Beta (β) Receptors: G protein–coupled receptors responsive to norepinephrine and epinephrine.

• Norepinephrine: Major neurotransmitter of the autonomic sympathetic division of the PNS.

Amino Acids

Excitatory and Inhibitory Amino Acids

• Glutamate: Main excitatory neurotransmitter in the CNS; depolarizes target cells.

• Aspartate: Excitatory neurotransmitter in the brain.

• GABA (γ-aminobutyric acid): Main inhibitory neurotransmitter in the brain; hyperpolarizes target cells by opening Cl- channels.

• Glycine: Inhibitory neurotransmitter in the CNS.

Glutamate Receptors

• AMPA Receptor: Alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor; mediates fast excitatory synaptic transmission.

• NMDA Receptor: N-methyl-D-aspartate receptor; involved in synaptic plasticity and memory function.

• Co-agonists: Glycine and D-serine enhance the excitatory effect of glutamate at NMDA receptors.

Other Neurotransmitters

Peptides, Purines, Gases, and Lipids

• Peptides: Examples include Substance P and opioid peptides, which modulate pain and other functions.

• Purines: ATP and AMP act as neurotransmitters in the CNS.

• Gases: Nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) diffuse across cell membranes to act as signaling molecules.

• Lipids: Eicosanoids and endogenous ligands for cannabinoid receptors.

Events at the Synapse

Kiss-and-Run Pathway

• Vesicle Fusion: Synaptic vesicles fuse with the presynaptic membrane at the fusion pore.

• Neurotransmitter Release: Neurotransmitters pass through the channel into the synaptic cleft.

• Vesicle Retrieval: Vesicles pull back from the fusion pore for reuse.

Major Neurocrines Table

Comparison of Major Neurocrines, Receptors, and Actions

Chemical	Receptor	Type	Receptor Location	Key Agonists, Antagonists, and Potentiators
Acetylcholine (ACh)	Nicotinic (nAChR)	ICR (Na+, K+)	Skeletal muscle, autonomic neurons, CNS	Agonist: nicotine Antagonist: curare, alpha-bungarotoxin
Acetylcholine (ACh)	Muscarinic (mAChR)	GPCR	Smooth muscle, cardiac muscle, CNS	Agonist: muscarine Antagonist: atropine, scopolamine
Norepinephrine (NE)	Adrenergic (α, β)	GPCR	Smooth and cardiac muscle, glands, CNS	Agonist: phenylephrine, isoproterenol Antagonist: propranolol, phentolamine
Dopamine (DA)	Dopamine (D1, D2)	GPCR	CNS	Agonist: bromocriptine Antagonist: haloperidol
Serotonin (5-HT)	Serotonergic (5-HT)	ICR (Na+, K+), GPCR	CNS	Agonist: sumatriptan Antagonist: LSD
Histamine	Histamine (H1)	GPCR	CNS	Antagonist: diphenhydramine (Benadryl)
Glutamate	Glutaminergic ionotropic (AMPA, NMDA)	ICR (Na+, K+)	CNS	Agonist: quisqualate Potentiator: glycine
GABA (γ-aminobutyric acid)	GABA	ICR (Cl-), GPCR	CNS	Agonist: muscimol Antagonist: bicuculline
Glycine	Glycine	ICR (Cl-)	CNS	Agonist: glycine Antagonist: strychnine
Adenosine	Purine (GPCR)	GPCR	CNS	Antagonist: caffeine
Gases (NO, CO, H2S)	None	N/A	N/A	N/A

Key Equations

• Nernst Equation: Used to calculate the equilibrium potential for a particular ion across a membrane. $E = \frac{RT}{zF} \ln \left( \frac{[\text{ion}]_{\text{outside}}}{[\text{ion}]_{\text{inside}}} \right)$

• Goldman-Hodgkin-Katz Equation: Used to determine the resting membrane potential considering multiple ions. $V_m = \frac{RT}{F} \ln \left( \frac{P_{K^+}[K^+]_{\text{out}} + P_{Na^+}[Na^+]_{\text{out}} + P_{Cl^-}[Cl^-]_{\text{in}}}{P_{K^+}[K^+]_{\text{in}} + P_{Na^+}[Na^+]_{\text{in}} + P_{Cl^-}[Cl^-]_{\text{out}}} \right)$

Additional info: Equations and some receptor details were inferred for completeness and academic context.