Neurotransmission Flashcards
Neurotransmission
The transmission of information between neurons- typically involves neurons releasing neurotransmitters into the synapse
The language of the brain is
Electrochemical. Electrical from dendrite to terminal, chemical from terminal to dendrite. Drugs typically work on the chemical part of this process
Resting membrane potential
When the cell is at rest it has a slightly negative charge (-70 mV), the charge is due to potassium and organic anions. Baseline charge
Extracellular environment
Has a positive charge- charge is due to sodium and chloride (negative) ions
How does the cell regulate its membrane potential at rest?
Sodium-potassium pumps regulate the exchange of sodium and potassium. 3 sodium exit and 2 potassium enter, maintaining the slightly negative charge. Uses ATP
Diffusion
Ions want to be evenly distributed throughout the extracellular and intracellular fluid. Two potassiums don’t want to be too close to each other. Ions travel from high to low concentration
Electrostatic pressure
positive charges repel positive charges, negative charges repel negative charges, and positive and negative charges attract
When does depolarization occur?
At the threshold of excitation (-55 mV)
Depolarization
Sodium channels open and Na+ rushes into the cell- charge becomes more positive. Later, K+ channels open and K+ leaves the cell. There is a reduced difference between the positive and negative charge on each side of the membrane
Action potential
Occurs at the axon hillock. Occurs quickly- the neuron “fires” and the signal travels down the axon. Ends immediately after the sodium channels close
Repolarization
Na+ is pushed out of the cell until the channel closes at +30 mV. K+ channels open slowly, and K+ continues to leave. Charge becomes more negative, back toward baseline
Hyperpolarization
K+ channels are slow to close, so K+ keeps leaving the cell and the membrane potential becomes too negative. The sodium potassium pump re-establishes the baseline voltage
Nodes of Ranvier
Gaps in the myelin sheath that are rich in sodium channels. Allows the action potential to travel down long axons without losing charge and regenerates the action potential. Allows for saltatory conduction because the action potential looks like it’s jumping
Electrical potential
Difference between the electrical charge within a neuron vs the electrical charge of the environment outside of the neuron
Ion channels
Allow ions to move in and out the cell, influencing charge. Ions can’t move in and out of the cell by themselves
Excitatory postsynaptic potential
Slightly depolarizes the membrane due to the binding of neurotransmitters. Can cause an action potential if enough of them occur to bring the voltage to -55 mV
Inhibitory postsynaptic potential
Slightly hyperpolarizes the membrane, making it more negative and less likely to fire
Voltage gated channels
The opening and closing of these channels depend on local potential changes. Describes potassium and sodium channels. Sodium channels open in response to depolarization
Sodium-potassium pump
A neuronal membrane mechanism that brings 2 potassium ions into the neuron and removes 3 sodium from the neuron. Uses ATP because the ions are moving against their concentration gradient. Maintains the negative charge of the cell
All or none law
The magnitude of an action potential is independent from the magnitude of the potential change that elicited the action potential- doesn’t depend on the strength of the stimulus
Refractory period
The period of time after an action potential when the neuron is less likely (or unable) to produce an action potential- occurs during hyperpolarization
Hodgkin Huxley model
Performed experiments on the axon of a squid. Found that specific voltage dependent ion channels (sodium and potassium) control the flow of ions through the cell membrane
How do cerebral neurons differ from motor neurons?
Many neurons fire continuously even without input. Some don’t have axons or action potentials.
In the cerebral cortex, the action potentials of different cells differ in terms of (3)
- Amplitude
- Duration
- Frequency
Neurotransmitters
Signaling chemicals that are synthesized within neurons, are released from neuron, and have effects on neurons or other cells. They chemically transmit information across the synapse
Synaptic vesicles
Store and protect neurotransmitters after synthesis in the soma. They protect neurotransmitters from being destroyed by enzymes and prevent neurotransmitters from being released prematurely. Neurotransmitters stored in vesicles can be immediately released during neurotransmission
Vesicular transport in the neuron
Vesicles already in the axon store small molecule neurotransmitters, and vesicles in the soma store large molecular neurotransmitters. Microtubules in the axon transport vesicles from the soma to the axon terminal
Calcium and release of neurotransmitters
An action potential triggers voltage gated calcium channels to open, and calcium enters the axon terminal. Calcium causes exocytosis. The vesicles fuse to the axon terminal membrane and neurotransmitters are released to the synapse
Neurotransmitter receptors
Neurotransmitters bind to receptor proteins on the postsynaptic terminal- when neurotransmitters bind, the proteins undergo a conformation change and cause changes in the neuron
Catabolism
Enzymes can break down neurotransmitters into metabolites to end neurotransmission and prevent the neurotransmitter from binding to other receptors
Reuptake
Membrane transporters on axon terminals return neurotransmitters to the axon terminal. Vesicles can store the neurotransmitters for later release. Like recycling for neurotransmitters
Glial cells function in ending neurotransmission
Neurotransmitters can be transported from the synaptic cleft into an astrocyte. Enzymes in the glial cell catabolize the neurotransmitters
Mechanisms of ending neurotransmission (3)
- Catabolism
- Reuptake
- Transport into glial cells
Binding site
A neurotransmitter will fit into a specific postsynaptic receptor like a key into a lock. However, other chemicals can imitate neurotransmitters
Ligand
A chemical that fits a binding site of a receptor- can activate the receptor or stop a neurotransmitter from binding
Receptors
Proteins located in neuron membranes that can be bound to and activated by neurotransmitters. Neurotransmitters are specific to receptors
Agonists
A drug that facilitates or enhances the effects of a particular neurotransmitter on the postsynaptic cell
Antagonist
A drug that opposes or inhibits the effects of a particular neurotransmitter on the postsynaptic cell
Ionotropic receptors
Receptors are coupled to ion channels- when the ion binds to the receptor, it causes the channel to open. Sometimes, a receptor opens a channel that causes positively charged particles to enter. This is excitatory and makes it more likely to have an action potential. Other times, receptors open ion channels that make negatively charged ions enter the cell. This is inhibitory and makes it more difficult for the neuron to have an action potential. They are ligand gated ion channels, with the neurotransmitter acting as a ligand
Structure of ionotropic receptors
Made up of subunits that span the neuronal membrane. The subunits form a ring that makes a channel. The shifting of these subunits causes the channel to open/close. They open when a neurotransmitter binds and close when the neurotransmitter leaves
Metabotropic receptor
Physically separated from parts of the neuron where the receptor exerts its effects. They typically use a G protein to convey effects to other channels or parts of the neuron- the receptors cause activation/release of G proteins. These receptors are slower acting (delayed by ms) and are long lasting.
G protein
Resides in the neuron in close proximity to the receptor. Consists of 3 subunits that are attached to each other until a neurotransmitter activates the receptor. Activating the receptor causes the G protein to separate into 2 sections. When the subunits return to a 3 subunit state, the receptor is deactivated
Possible effects of G proteins (2)
- Can act like an ionotropic receptor
- Can initiate synthesis of AMP (adenosine monophosphate)- second messengers
Second messenger
An intracellular signaling molecule produced following the activation of another protein by an extracellular molecule (a neurotransmitter). Includes cAMP and calcium. The neurotransmitter that activated the receptor can be thought of as the first messenger
Neurochemical mechanisms of drug action (8)
- Neurotransmitter synthesis
- NT transport
- Neurotransmitter storage
- NT release
- NT degradation
- NT reuptake
- Receptor activation
- Receptor blocking
Neurotransmitter synthesis
Increase or decrease the synthesis of neurotransmitters
Neurotransmitter transport
Interfere with the transport of neurotransmitter molecules to the axon terminals- it can’t be released into the synapse
Neurotransmitter storage
Interfere with the storage of neurotransmitters in the vesicles of the axon terminal- neurotransmitters can’t be protected and may be degraded by enzymes
Neurotransmitter release
Cause the axon terminals to release neurotransmitter molecules into the synapse prematurely- influences postsynaptic signaling
Neurotransmitter degradation
Influence the breakdown of neurotransmitters by enzymes
Neurotransmitter reuptake
Block the reuptake of neurotransmitters into the axon terminals- more NT is available for the postsynaptic neuron
Receptor activation
Activate a receptor site by mimicking a neurotransmitter- agonists/antagonists
Receptor blocking
Cause a receptor to become inactive by blocking it- postsynaptic neuron isn’t signaled
Acetylcholine (ACh)
ACh neurons are called cholinergic neurons, and their receptors are called cholinergic receptors. ACh is a mostly excitatory neurotransmitter. Highly involved in sensory systems and motor movement. It is the main NT released by PSNS neurons
2 classes of ACh receptors
- Nicotinic receptors
- Muscarinic receptors
Nicotinic receptors
An ACh receptor that is exclusively acted on by nicotine. They are ionotropic and excitatory- they cause an influx by positively charged sodium, potassium, and calcium ions. Nicotine is an ACh agonist
Muscarinic receptors
ACh receptor that is acted on by muscarine, a toxin found in mushrooms. All of these receptors are metabotropic and can be inhibitory or excitatory
Alzheimer’s disease
A neurological disorder characterized by impairments in cognition, motivation, language production, and comprehension. Neuronal damage occurs most severely in the basal forebrain and causes degeneration of more than two thirds of its cholinergic neurons
Monoamine neurotransmitters (4)
- Norepinephrine
- Dopamine
- Serotonin
- Epinephrine- did not cover this one in class
Dopamine
All dopamine receptors are metabotropic, and can be inhibitory or excitatory depending on the family of receptors. They are mostly found in the hypothalamus, ventral tegmental area, and substantia nigra. Responsible for coordinated motor movements and anticipation of pleasurable experiences- dopamine levels increase as you approach a pleasurable event
L-DOPA
Increasing L-DOPA levels increases dopamine levels because L-DOPA is converted to dopamine. Dopamine can’t cross the blood brain barrier so L-DOPA is used to treat people with Parkinson’s disease. It compensates for the loss of dopamine by allowing the remaining dopamine neurons to produce more dopamine
Norepinephrine
NE neurons are called noradrenergic neurons. Its receptors are all metabotropic but can be excitatory or inhibitory. In the brain, receptors are found in the cerebral cortex, hippocampus, and amygdala. It regulates hunger, alertness, and arousal
Serotonin
Receptors can be metabotropic and excitatory or inhibitory. There is also one class of ionotropic receptor (5-HT3) that is excitatory. Their cell bodies are located in the raphe nuclei in the brainstem, and serotonin pathways terminate in structures throughout the brain. Found throughout the brain and gut, implicated in sleep and mood- 90% of serotonin receptors are in the gut
Too much dopamine causes
Too much dopamine can cause hallucinations and delusions- blocking dopamine solves these but can cause tardive dyskinesia. Can occur during L-DOPA treatment
Glutamate
An amino acid that acts as an excitatory neurotransmitter. Involved in learning and memory. Receptors are located in the basal ganglia and hippocampus. Drugs like ketamine and PCP act on glutamate receptors
GABA
An amino acid that acts as an inhibitory neurotransmitter- it is one of the most abundant neurotransmitters in the brain. It causes the cell to hyperpolarize, channels allow negatively charged chloride ions to enter the cell and cause IPSPs. This means it would take more excitatory NTs to get the neuron to fire. Barbiturates and tranquilizers act on GABA receptors by increasing the amount of GABA in the brain
Glutamate receptors (4)
- AMPA- ionotropic
- NMDA- ionotropic
- Kainate- ionotropic
- mGluR- metabotropic
Ionotropic glutamate receptors
When activated, AMPA, NDMA, and kainate allow positively charged ions, like sodium and calcium, to enter the neuron. The influx of positive charge causes excitatory postsynaptic potentials
mGluR receptors
There are 3 groups of these receptors. Group 1 receptors enhance neuronal activity- activate a G protein and start a cascade of other effects. Group 2 and 3 activate G proteins that diminish further signaling in the neuron
Glutamate receptors on astrocytes
Glutamate receptors (AMPA and mGluR) are found on glial cells. Activating glutamate receptors on astrocytes allows calcium to enter the cell. It allows other processes to occur in astrocytes, like the release of glutamate that binds to neurons. Astrocytes can therefore influence neurotransmission directly
GABA receptors (2)
GABAa (ionotropic) and GABAb (metabotropic). Both are inhibitory. GABAa has been studied the most and is responsible for the effects of many CNS depressants, like alcohol, barbiturates, and benzodiazepines
