two major types of neurotransmitters:  fast and slow 

Whether a neurotransmitter’s action is fast or slow depends upon the type of receptor that it binds to.

Whether a neurotransmitter’s action is fast or slow depends upon the type of receptor that it binds to.

Ligand gated ion channels 

G Protein Coupled receptor 

Ligand gated ion channels = Ionotropic receptors

G Protein Coupled receptor = Muscarinic

1.         Binding of the neurotransmitter activates the G protein which then binds to the ion channel and opens the gate.

2.         Binding of the neurotransmitter activates the G protein which activates an enzyme.  The enzyme catalyzes the production of a second messenger that interacts with the ion channel and opens it.  An example of this type of receptor is the beta adrenoceptor.  Binding of NE to the beta receptor activates adenylyl cyclase that, in turn, generates cAMP which opens the channel.

three criteria that define a substance as a neurotransmitter:  

1.         The substance must be present within the presynaptic neuron.

2.         The substance must be released in response to presynaptic depolarization, and the release must be Ca2+-dependent.

3.         Specific receptors for the substance must be present on the postsynaptic cell. 

• Ligand binds to the heterotrimer
• alpha protein picks up a phosphate
• SECOND MESSENGER binds to ion channel & opens it

Once released:

-bind to receptor on post-synaptic terminal

-biotransformed by enzyme (COMT/cholinesterase)

*COMT-->NE

*Cholinesterase-->Ach

-Reuptake into receptor that just released it, open up K channels to repolarized it.

.  Binding of neurotransmitter to these receptors opens a gate at the base of the channel, thus allowing ions to flow into or out of the neuron according to their concentration gradients.

Nicotinic sites

Long term potentiation

process that underlies learning and memory.  LTP is a long-lasting enhancement of synaptic transmission at AMPA receptors (ionotropic glutamate receptors)

Glutamate binds to several different sub-types of receptors on the post-synaptic neuron. Two of these sub-types, the receptors for AMPA and NMDA, are especially important for LTP. 

The NMDA receptor is also paired with an ion channel, but this channel admits calcium ions into the post-synaptic cell. When this cell is at resting potential, the calcium channel is blocked by magnesium ions (Mg2+), so that even if glutamate binds to the receptor, calcium cannot enter the neuron. For these magnesium ions to withdraw from the channel, the dendrite’s membrane potential must be depolarized.

the post-synaptic neuron becomes depolarized following the sustained activation of its AMPA receptors! The magnesium then withdraws from the NMDA receptors and allows large numbers of calcium ions to enter the cell.

This increased concentration of calcium in the dendrite sets off several biochemical reactions that make this synapse more efficient for an extended period.

Inhibitory amino acid neurotrasmitter

Blocks Na & Ca Channels

Part of the receptor is modulatory site, when something binds to it, it potentiates receptor, prolongs opening of channel

There are two types of GABA receptors:  GABA_A and GABA_B:

• GABA_A receptors are ligand-gated ion channels.  When activated, they increase membrane permeability to Cl-, thus inducing Cl- influx into the cell.  This Cl- influx induces hyperpolarization of the cell membrane and prevents propagation of action potentials. In contrast,

• GABA_B receptors are G protein-coupled receptors that are located on both presynaptic and postsynaptic neurons. 

Drugs that bind to GABA_A receptors include benzodiazepines and barbiturates. 

Benzodiazepines bind to a regulatory site on the GABA_A receptor and increase the affinity of GABA for the receptor’s binding site.  The result is an increase in the frequency of chloride channel opening. Anticonvulsant barbiturates, such as phenobarbital, potentiate GABAergic inhibition (although they bind to a different site on the GABA receptor than benzodiazepines) and have anticonvulsant and sedative properties. 

In contrast, GABA_B receptors are G protein-coupled receptors that are located on both presynaptic and postsynaptic neurons.

Activation of GABA_B receptors can either close Ca2++ channels or open K+ channels (produces hyperpolarization).  Either effect will inhibit neurotransmitter release. 

In the CNS, NE pathways originate in the brain stem in lows cerulius

in lower brain stem for stress respons. 

NE controls arousal and mood, and regulates BP.

Dopamine

majority of dopamine is secreted by neurons that originate in the substantia nigra. regulating mentation and mood), the nigrostriatal tract (extrapyramidal function)

Tyrosine--> dopa--> dopamine

D1- increase CAMP-->GPCR

Excitatory

D2 - Decrease CAMP

keeps K open

Keeps Ca closed

-depolarizing current, Na channels open, more (+)--> opens voltage gated Ca channels-->vesicle--> exocytosis--> dopamine in synaptic cleft

1. bind to DA receptor

2. biotransformed by COMT

3. Taken back up into neuron by MAOI's 

4. DA receptro on presynaptic terminal, shut it off by repolarizing K & Cl.

5. Extraneuronal degradation of DA: COMT

6: intraneuronal degradation of DA: MAO

Serotonin has strong inhibitory effects in most areas of the CNS. 

secreted specifically by the large pyramidal cells of the motor cortex, by several different neurons in the basal ganglia, and by the motor neuron that innervates the skeletal muscles. In most instances, Ach has an excitatory effect.

In Parkinson’s disease, there is a loss of dopaminergic neurons.  Since dopamine (an inhibitory transmitter) and acetylcholine (an excitatory transmitter) are normally maintained in a balance, the loss of dopamine tips the balance in favor of Ach. The excess Ach, results in dyskinesias (abnormal involuntary movement), rigidity, and resting tremors.  Many drugs can cause parkinsonian symptoms, such as the anti-psychotic drugs that block dopamine receptors.

alpha 2 agonist(inhibits NE release from CNS, centrally decreases BP.

Clonidine binds to alpha-2 receptors in the medulla, thus inhibiting sympathetic outflow.   Interestingly, clonidine is also effective in the management of autonomic symptoms associated with opioid withdrawal.  

peripherally constricts-good for allergies.