Nerv Sys Cell Communication

Chemical synapses

are the bridge between two neurons

Pre-synaptic cell

• action potential arrives at axon terminal

• Voltage-gated Ca2+ channels open

• Ca2+ influx triggers exocytosis of Neurocrine signal molecules

→ neurotransmitters, neuromodulators, neurohormones

Post-synaptic

• Is the target cell (another neuron [dendrites], muscle fiber, etc)

• Must have receptors for the Neurocrine secreted onto it

How synaptic transmission occurs

When the action potential reaches axon terminal…

• Voltage gated channels of Ca++ open → Ca++ influxes → cues exocytosis of neurotransmitter → neurotransmitter crosses synapse → neurotransmitter interacts with a receptor (could be an enzyme, g-protein coupled receptor, etc) → leading to a cell response (EPSP or IPSP)

Post synaptic cell response

Neuron’s goal is to communicate w/ a target cell by sending a Neurocrine signal

• The goal was to get that targe cell to change function or perform work

So, what happens when the signal molecule reaches an adjacent neuron or muscle cell?

that

Termination of Neurocrine action

Various mechanisms!

• Re-uptake by pre-synaptic cell or removal by glial cells

• Inactivating enzyme

• Diffusion away from site

Selective Serotonin Reuptake Inhibitors (SSRIs) increase serotonin concentration at CNS synapses by blocking the serotonin transporter (SERT) protein, which inhibits the reuptake (recycling) of serotonin from the synaptic cleft back into the presynaptic neuron. This blockage causes increased serotonin availability in the synaptic cleft, strengthening neurotransmission and alleviating depressive symptoms

7 classes of Neurocrines that differ by chemical structure and function

Remember that each Neurocrine can have multiple receptors!

• Acetylcholine

• Monoamines

• Amino acids

• Purines

• Gases

• Peptides

• Lipids

Acetylcholine (ACh) acts as both a neurotransmitter and neuromodulator

• In a category all by itself

• An important neurotransmitter and neuromodulator in the CNS

• ALWAYS an excitatory neurotransmitter for skeletal muscles at the neuromuscular junction

• Used by parasympathetic branch of ANS to control body organs

→ that influence can be excitatory or inhibitory depending on the receptor ACh binds to

• Formed from acetyl CoA and choline

Cholinergic receptors

Remember that the specific receptor type ultimately determines the action of the target cell (depolarize and activate or hyperpolarize and inactivate)

• There are 2 categories of cholinergic receptors

• Their natural neurotransmitter is acetylcholine

→ Nicotinic receptors

→ Muscarinic receptors

Nicotinic receptors

• are located on skeletal muscle and in PNS and CNS

• Two subtypes: Nm and Nn

→ nicotinic N sub M and nicotinic N sub n

• both are chemically gated receptor channels

→ allow influx of Na+ and efflux of K+ (monovalent cation channels)

→ also referred to as “ionotropic” channels

• Always excitatory because more Na+ influxes than K+ effluxes

Muscarinic receptors

• are located throughout the CNS and PNS

• Five subtypes: M1, M2, M3, M4, M5

• They are G-protein coupled receptors

• Also referred to as “metabotropic” receptors

• They can be excitatory or inhibitory depending on the intracellular cascade

The “lifecycle” of acetylcholine

• Note how ACh is synthesized

→ The enzyme that synthesizes ACh at step 1 is called choline acetyltransferase

There are two types of receptors for ACh

• Nicotinic - a monovalent cation channel

• Muscarinic - A GPCR

Note its inactivating enzyme in the synaptic cleft

acetylcholinesterase (AChE)

Note re-cycling of choline

symport!

• Secondary active transport

• Na+ going down concentration gradient, and Choline going against concentration gradient

Monoamine neurotransmitters, neuromodulators, and neurohormones

• this category is called “amines”

• These Neurocrines are derived from single amino acids

• Catecholamines: derived from the amino acid tyrosine

→ they include…

• Epinephrine

• Norepinephrine

• Dopamine

Epinephrine

ALWAYS a neurohormone, which is secreted form modified, adrenergic neurons called chromaffin cells in the adrenal medulla

Norepinephrine

a neurotransmitter and neuromodulator secreted by noradrenergic neurons; also acts as a neurohormone when secreted from the adrenal medulla

Dopamine

a neurotransmitter and neuromodulator secreted from dopaminergic neurons; also acts as a neurohormone when secreted from the adrenal medulla

Others….

• Serotonin and melatonin (the indolamines) are neurotransmitters and neuromodulators made from tryptophan

• Histamine is a neurotransmitter and neuromodulator made from histidine

Adrenergic receptors

There are two subcategories of adrenergic receptors

• Natural Neurocrines (catecholamines)

• Alpha receptors + beta receptors

Catecholamines

norepinephrine or epinephrine can bind

Alpha receptors and beta receptors

• Alpha receptors: ⍺1 and ⍺2

• Beta receptors: β1, β2, & β3

→ these receptors differ in their affinity for epinephrine and norepinephrine (indicated by the colors in the adjacent diagram)

All adrenergic receptors are G-protein coupled receptors, so…

so… they too can be either excitatory or inhibitory depending on the intracellular cascade

Amino Acid neurotransmitters

Rather than being used in protein synthesis, several amino acids are packaged into secretory vesicles within neurons for release as neurotransmitters

• Glutamate

• Aspartate

• Gamma-aminobutyric acid (GABA): Inhibitory

• Glycine

Glutamine

Excitatory → Used throughout the CNS

Aspartate

Excitatory → used only in the brain

Gamma-aminobutyric acid (GABA): Inhibitory

Used only in the brain, a derivative of glutamine

-→ released in large amounts whenever u drink alc or do drgz

Glycine

• Inhibitory → used only in the spinal cord

• May also be excitatory in some cases

Glutamine is particularly important for…

for the strengthening of neural circuits based on how much they are used, so it is critical for learning and memory

Other neurocrines…

• Peptide neurocrines

• Purine neurocrines

• Gas neurocrines

• Lipid neurocrines

Peptide neurocrines

• Substance P and opioid peptides (ex: endorphins and enkephalins)

→ part of the pain perception and pain suppression pathways in your nervous system

• Vasopressin (antidiuretic hormone)

→ part of water balance

• Oxytocin

→ involved in childbirth (stimulates uterine contractions) and lactation in females, along with social bonding and secxual attraction in males and females

Purine neurocrines

• Adenosine, AMP, and ATP

→ these are all important neurocrines in sleep/wake cycles and attentiveness

→ caffeine blocks adenosine! keeps u awake longer

Gas neurocrines

• Nitric Oxide (NO) and Carbon Monoxide (CO)

→ stimulate localized vasodilation, to bring more nutrients to and increase waste pick-up from hard-working neurons

Lipid neurocrines

• Some eicosanoids are natural ligands for cannabinoid (CB1) receptors in the brain

• This receptor also binds exogenous ligands like ∆9-tetrahydrocannabinoid, which is the main psychoactive ingredient in maryjane