PT 22 LEC: Organization, Basic Functions of Synapses, and Neurotransmitters

neuron

basic functional unit

special feature of most synapses

forward direction

dendrites

various numbers of branching projections of the soma that extend as much as 1 millimeter into the surrounding areas of the cord; incoming signals

axons

extends from the soma into a peripheral nerve that leaves the spinal cord; output via single one leaving neuron

soma

body of neuron

presynaptic terminals

- varied anatomical forms, but mostly small round or oval knobs

- 80-95% of terminals found on the dendrites and 5-20% found on the soma

synaptic cleft

space between pre- and post-synaptic neuron

synapses

- junction point from one neuron to next

- determine direction of nervous signals

- can be inhibitory or facilitatory

- selective action

pyramidal cells

motor function; biggest

Purkinje fibers

cerebellum; multiple axons

electrical synapses

- 3.5 nm distance between pre- & post-synaptic cell membrane

- cytoplasmic continuity present

- flow thru gap junctions

- ionic current

- virtually absent synaptic delay

- bidirectional transmission

chemical synapses

- 30-50 nm distance between pre- & post-synaptic cell membrane

- no cytoplasmic continuity

- flow thru presynaptic active zones & vesicles; postsynaptic receptors

- chemical transmitter

- significant synaptic delay

- unidirectional transmission

neurotransmitter

one way conduction; binds to receptor proteins at the post synaptic neuron

binding component

- produce outwards

- binds NTM from presynaptic terminals

ionophore cation channel

- negatively charged

- excitatory

- allow Na+ ions to pass

ionophore anion channel

- positively charged

- inhibitory

- allow Cl- ions to pass

ionophore second messenger system

- causes prolonged effect needed by NS

- in post synaptic neuron

ionotropic receptor

- ligand-gated ion channel

- opens when NTM attaches

- independent of second messenger

- short latency with rapid response

- post synaptic

2 types of NTM receptors

ionotropic & metabotropic

metabotropic receptor

- second messenger system; G protein-coupled receptor

- causes opening of ion channels when activated

- G protein activates secondary messengers

- takes LONGER to effect & MORE WIDESPREAD vs ionotropic

- pre- & post-synaptic

metabotropic receptor second messenger coupling

receptor accepts NTM, then post-synaptic cell finds the G-protein; alpha gene which

(1) opens channel to hyperpolarize cell

(2) triggers production of ATP via attachment to enzymes

(3) activates one or more intracellular enzymes

(4) activates gene transcription

acetylcholine (ACh)

- neuromuscular junctions & ANS; mainly secreted by pyramidal cells

- CHOLINERGICS

- excitatory; some inhibitory effects like in the heart via vagus nerve

- memory & learning

Alzheimer's Disease

associated with breakdown of ACh neurons

ACh commonly binds with

nicotinic & muscarinic receptors; CHOLINERGIC RECEPTORS

nicotinic receptors

- IONOTROPIC

- muscle cells, CNS, ANS

- integral for movement

muscarinic receptors

- METABOTROPIC

- CNS, PNS of heart, lungs, upper GIT, & sweat glands

- uses G-protein

ACh synthesis

- ACh broken down by acetylcholinesterase

- results in choline & acetate

- choline transported back to presynaptic neuron for resynthesis

- acetate excreted or reused as Acetyl CoA

- choline + Acetyl CoA in presynaptic neuron synthesize new ACh via acetyl transferase

norepinephrine (NE)

- secreted by brain stem, hypothalamus, pons, and most postganglionic

- excitatory but can be inhibitory

- noradrenergic receptors

- "high alert"; main NTM for SNS

synthesis of NE & dopamine

- hydroxylation of phenylalanine into tyrosine via enzyme phenylalanine hydroxylase

- hydroxylation of tyrosine into L dopamine via enzyme tyrosine hydroxylase

- decarboxylation of L dopamine into dopamine via enzyme DOPA decarboxylase (conversion in the cytoplasm)

- hydroxylation of dopamine into NE via enzyme dopamine monooxygenase (conversion occurs in NTM vesicles)

epinephrine (EPI)

- produced by adrenal glands & some neurons

- comes from NE; related to adrenaline

- adrenergic receptors

- ANS; fight or flight

EPI pen

used to treat cardiac arrest, anaphylaxis, hypoglycemia, bronchospasm

epinephrine synthesis

methylation of NE into EPI via enzyme phenylethanolamine N methyltransferase

dopamine

- secreted by neurons that originate in the substantia nigra

- usually inhibitory

- dopaminergic receptors

- increased in schizophrenia; decreased in Parkinson's

glycine

- secreted mainly at synapses in SC, brainstem, retina

- process motor & sensory info that permits movements, vision, and audition

- inhibitory transmitter

- glycinergic receptor

glycine synthesis

- Non essential amino acid (biosynthesized from amino acid serine hydroxymethyltransferase)

- Catalyzed by glycine synthase

- Can be readily converted

Gamma-aminobutyric acid (GABA)

- secreted by nerve terminals in CNS

- major helper of dopamine

- PRIMARY INHIBITORY NTM OF CNS

- comes from glutamate

- regulates muscle tone

- GABAergic receptors

GABA synthesis

glutamate synthesized into GABA via enzyme glutamate decarboxylase

glutamate

- secreted by presynaptic terminals in many sensory pathways entering CNS or cerebral cortex

- PRIMARY EXCITATORY NTM IN CNS

- glutaminergic receptors

- learning & memory

Lou Gehrig's disease (ALS)

- excess glutamate (toxic effect)

- leads to cell hyperactivity → cell death

glutamate synthesis

- Glutamate converted to glutamine (via glutamine synthetase)

- glutamine taken into the presynaptic terminal for resynthesis (packaged back into the synaptic vesicles)

- metabolized back into glutamate via glutaminase

serotonin

- secreted by nuclei that originate in median raphe of brain, SC, hypothalamus

- inhibitor of pain pathways

- emotions & moods

- serotonergic receptors

serotonin synthesis

- tryptophan becomes hydroxytryptophan via enzyme tryptophan hydroxylase

- becomes serotonin via enzyme L-amino acid decarboxylase

nitric oxide

- gaseous NTM

- secreted by nerve terminals in areas responsible for long-term behavior & memory

- not preformed and stored in vesicles in presynaptic terminals; instead synthesized almost instantly & diffused in seconds

- changes intracellular metabolism → modifies neuron excitability to become longer

- does NOT alter membrane potential

Neuropeptides

- synthesized in ribosomes

- vesicles containing them are autolyzed; not reused

- released in PREsynaptic terminals

- more potent w/ prolonged actions

Beta endorphins

opioid neuropeptide found in neurons of PNS & CNS; agonist of opioid receptors with analgesic effects

Endogenous opiates

naturally produced in CNS & usually found in the pituitary gland

Leu-enkephalin (leucine enkephalin)

- adrenal medulla; agonists of mu & delta opioid receptors with analgesic effects

- regulates nociception

Met enkephalin (methionine enkephalin)

also known as opioid growth factor (OGF); short duration of action with analgesic & anti-depressant effects

Substance P

- neurotransmitter & neuromodulator; first-responder to noxious stimuli (associated with inflammatory response)

- potent vasodilator but dependent on nitric oxide

- neurokinin 1

Nernst potential

Equilibrium potential or reverse potential; potential that exactly opposes movement of an ion

Nernst potential for sodium

+55mV to +65mV

Nernst potential for chloride

-65mV to -70mV

Nernst potential for potassium

-90m

EPSP

Positive increase in voltage above normal resting neuronal

potential (less negative); will reach AP if rises high enough

IPSP

Increase in negativity beyond normal resting membrane

potential; leads to hyperpolarization

Presynaptic inhibition

caused by inhibitory synapses at

the neuronal membrane (usually caused by GABA);

common in sensory fibers to minimize mixed or abnormal

signals

Spatial summation

increasing number of fibers being

Temporal summation

increasing rate of firing

Electrotonic current

- non-propagated potential with minor change in ionic

conducted

- current induced in nerve sheath without generation of a

new current; decremental

Decremental conduction

Decrease in membrane potential as it spreads

electrotonically along dendrites towards soma

factors affecting synaptic transmission

- repeated stimulation at rapid rate

- alkalosis

- acidosis

- hypoxia

- drugs

- synaptic delay