Chapter 4: Neurophysiology, Neurotransmitters and the Nervous System Part III - Neurochemistry

first step of neurotransmitter action

neurotransmitter molecules are synthesized from precursors under the influence of enzymes

second step of neurotransmitter action

neurotransmitter molecules are stored in vesicles until their release into the synaptic cleft after an action potential arrives

third step of neurotransmitter action

neurotransmitter molecules that leak from their vesicles are destroyed by enzymes

fourth step of neurotransmitter action

action potentials cause vesicles to fuse with the presynaptic membrane and release their neurotransmitter molecules into the synapse

fifth step of neurotransmitter action

released neurotransmitter molecules bind with autofirst step of neurotransmitter action receptors and inhibit subsequent neurotransmitter release

sixth step of neurotransmitter action

released neurotransmitter molecules bind to postsynaptic receptors

seventh step of neurotransmitter action

released neurotransmitter molecules are deactivated by either reuptake or enzymatic dgonaegradation

agonistic drug effects

drug increases the synthesis of neurotransmitter molecules, increases the number of neurotransmitter molecules by destroying degrading enzymes, increases the release of neurotransmitter molecules from terminal buttons. binds to auto receptors and blocks inhibitory effect on neurotransmitter release, and ends to postsynaptic receptors and either activates them or increases the effect on them of neurotransmitter

antagonist drug effect

drug blocks synthesis of neurotransmitter molecules, causes neurotransmitter molecules to leak from vesicles and be destroyed by degrading enzymes, blocks the release of the neurotransmitter molecules from terminal buttons, activates auto receptors and inhibits neurotransmitter release, and is a receptor blocker; binds to postsynaptic receptors and blocks the effect of the neurotransmitter

drugs can function…

as agonists or antagonists at receptors

receptors

membrane proteins bound to and activated by neurotransmitters

autoreceptor

presynaptic receptor activated by neurotransmitters that are released from same axon terminal

drugs that are antagonists at receptors have

an agonistic effect with respect to synaptic communication

heteroreceptor

presynaptic receptor activated by neurotransmitters that are different from those released from axon terminal

presynaptic inhibition

opening of calcium channels is inhibitedat the presynaptic terminal, reducing neurotransmitter release.

presynaptic facilitation

opening of calcium channels is facilitated

calcium channels

must open to permit release of neurotransmitter

based on ____, receptors can be classified into two broad categories

structural and functional characteristics

categories of receptors

ionotropic receptors and metabotropic receptors

inotropic receptors

are comprised of multiple protein subunits which form an ion channel pore

metabotropic receptors

are individual (large) proteins (that traverse membrane multiple times) and are indirectly linked with ion channels on the plasma membrane of the cell through signal transduction mechanisms, often G proteins

differences ionotropic vs metabotropic receptors

inotropic are fast on/off, all or none on/off, triggers action potentials, made up of multiple interchangeable subunits — metabotropic are slower off/off, can amplify or dampen signals, triggers multiple post-synaptic events, including action potentials, monomers

G_s pathway

is a signaling pathway that stimulates adenylate cyclase, increasing the production of cyclic AMP (cAMP) and activating protein kinase A (PKA), which leads to various cellular responses.

second messengers are

small intracellular molecules that transmit and amplify signals inside a cell after a receptor is activated

first messenger

an extracellular signal binds to receptor on the cell membrane

example of second messenger

ion channel opening, enzyme activity, or gene expression

main steps in gene expression

1. transcription - DNA is copied into messenger RNA

2. translation - mRNA used as a template by ribosome to build a protein

CREB

(cAMP response element-binding protein) - a cellular transcription factor, it binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the genes

genes whose transcription are regulated by CREB include

c-fos

c-fos

a transcription factor that can promote the expression of AMPA receptor subunits

effector protein in Gs pathway

adenylate cyclasee

effector protein in Gq pathway

phospholipase C

effector protein in Gi pathway

adenylate cyclase inhibition

second messengers in Gs pathway

cAMP

second messengers in Gq pathway

DAG and IP₃

second messengers in Gi pathway

cAMP reduction

later effectors in Gs pathway

protein kinase A

later effectors in Gq pathway

protein kinase C from DAG and calcium release from IP3

what doe the Gs pathway do

increase protein phosphorylation

what does Gq pathway do

increase protein phosphorylation and activate Ca2+-binding proteins

what does Gi pathway do

decrease protein phosphorylation

physical proximity to parts of neuron where effects exerted (ionotropic receptor and metabotropic receptor)

ionotropic receptor- attached to ion channel; metabotropic receptor - separated from ion channels and other proteins

type of effect differences

ionotropic receptor - open ion channel, metabotropic receptor - uses G protein to activate ion channels and effector enzymes

duration of effect differences

ionotropic receptor - ends when neurotransmitter leaves binding site; metabotropic receptor - effector enzymes engage a cascade of events that persist after neurotransmitter leaves receptor

impact on a neuron differences

ionotropic receptor -influx of ions changes local potential; metabotropic receptor - can affect local potentials and other effects like enzyme regulation, gene expression and protein synthesis

what defines a neurotransmitter

1. synthesis

2. release

3. receptor action

4. inactivation

neurotransmitter synthesis

some neurotransmitters are transported from the cell nucleus to the terminal button , others made from building blocks imported into the terminal, are packaged into vesicles there

neurotransmitter release

in response to an action potential, the transmitter is released across the membrane by exocytosis

neurotransmitter receptor action

the transmitter crosses the synaptic cleft and binds to a receptor

neurotransmitter inactivation

the transmitter is either taken back into the terminal or inactivated in the synaptic cleft

neurotransmitter categories

amino acids, modified amino acids, monoamines, neuropeptides, gases

monoamines - neurotransmitters

indoleamines(serotonin) and catecholamines (dopamine, norepinephrine, epinephrine)

types of amino acid neurotransmitters

glutamate and gaba