The Brain Flashcards
What is an excitable cell?
A type of cell that is capable of generating and responding to electrical signals.
Can undergo rapid changes in their membrane potential, which allows them to transmit electrical impulses or action potentials.
What is the resting membrane potential?
~-70 mV in most neurones
Dependent on separation of charge across lipid bilayer membrane
What are action potentials?
Excitable cells can generate an action potential—a rapid, temporary reversal of the membrane potential that travels along the cell’s membrane.
An action potential is a large transient change in membrane potential and is an “all or none” response
This is what allows these cells to transmit signals over long distances (like in nerves) or trigger responses (like muscle contraction).
Action potentials are very rapid (as brief as 1–4 milliseconds) and may repeat at frequencies of several hundred per second
What is depolarisation?
Depolarization is the potential moving from RMP to less negative values
It occurs when sodium ions (Na⁺) rush into the cell, making the inside less negative (or more positive).
This is an essential process for action potentials in neurons and muscle contraction in muscle cells.
What is repolarisation?
Repolarization is the potential moving back to the RMP
It happens when potassium (K⁺) ions leave the cell, making the inside more negative again.
Repolarization is essential for resetting excitable cells (like neurons and muscle cells) so they can respond to new stimuli and transmit further electrical signals.
What is hyperpolarisation?
Hyperpolarization is the potential moving away from the RMP in a more negative direction
It usually happens after the action potential has passed through its peak and repolarization, where potassium ions continue to exit the cell.
It makes it harder for the cell to fire another action potential, contributing to the refractory period and preventing excessive or continuous firing of the cell.
Hyperpolarization helps regulate cellular activity, whether in neurons or muscles, to maintain proper function and prevent overstimulation.
How do nerve cells communicate?
Electrical signal: The neuron generates an action potential (an electrical impulse) that travels down its axon.
Chemical signal: At the axon terminal, the electrical signal triggers the release of neurotransmitters into the synapse.
Neurotransmitter action: These neurotransmitters bind to receptors on the next neuron (or muscle), either exciting or inhibiting it.
Summation: The postsynaptic neuron integrates all incoming signals to decide whether to generate its own action potential.
Neurotransmitter release by exocytosis
- Action potential arrives at the axon terminal.
- Voltage-gated calcium (Ca²⁺) channels open, allowing calcium ions to enter the presynaptic terminal.
- The rise in intracellular calcium triggers vesicle fusion with the presynaptic membrane via synaptotagmin and SNARE proteins.
- The vesicle releases its neurotransmitters into the synaptic cleft by exocytosis.
- Neurotransmitters bind to postsynaptic receptors, transmitting the signal to the next cell.
- The vesicle membrane is recycled via endocytosis
What are the two kinds of receptors?
ligand gated ion-channel
(‘ionotropic’ receptor)
G-protein coupled receptor (GPCR)
(‘metabotropic’ receptor)
What are the different types of G-coupled proteins receptors?
Gs and Gq: generally excitatory
Gi: generally inhibitory
What are the three types of synapses?
Axo-somatic
Axo-axonic
Axo-dendritic
Why are CNS disorders so hard to treat?
- Neurones are highly complex structures interconnected in complex networks
- Numerous synapses on each neurone
- Numerous neurotransmitters and receptors
- Multiple possible sites for dysfunction
- Multiple sites of possible intervention
- Even for a single neurotransmitter, numerous possible drug targets are possible
- But drugs are rarely selective
What are the sites of action of CNS drugs?
Neurotransmitter receptors (e.g., dopamine, serotonin, GABA, glutamate).
Ion channels (e.g., sodium, chloride, calcium, potassium channels).
Enzymes (e.g., acetylcholinesterase, MAO, COMT).
Reuptake transporters (e.g., serotonin, dopamine, and norepinephrine transporters).
Blood-brain barrier mechanisms that govern drug entry into the CNS.
Neuroinflammatory pathways and the immune system.
What is cerebrospinal fluid?
Cerebrospinal fluid (CSF) is a clear, colorless liquid that surrounds and cushions the brain and spinal cord, providing both mechanical and chemical protection. It compensates for changes in brain volume. It is produced by the chlorois plexus and is an aqueus solution of NaCl + glucose plus low concentrations of K+, Ca2+.
What is glutamate?
Glutamate is the most abundant excitatory neurotransmitter in the brain and central nervous system (CNS). It is responsible for stimulating neurons and facilitating communication between them.
It is involved in learning, memory, synaptic plasticity, and brain development.
However, excessive glutamate activity can lead to excitotoxicity, which is harmful and has been linked to various neurological disorders.
Glutamate receptors (such as NMDA, AMPA, and kainate receptors) mediate its effects.
What is GABA?
GABA (Gamma-Aminobutyric Acid) is the primary inhibitory neurotransmitter in the brain and spinal cord, playing a key role in reducing neuronal excitability and preventing excessive neural firing.
GABA acts through two main types of receptors: GABA-A receptors (ionotropic, fast inhibition) and GABA-B receptors (metabotropic, slower inhibition).
GABA is crucial for maintaining brain balance, regulating anxiety, sleep, cognitive function, and seizure prevention.
Drugs that modulate GABAergic activity, such as benzodiazepines and barbiturates, are commonly used in the treatment of anxiety, insomnia, and epilepsy.
GABA dysfunction is implicated in several neurological and psychiatric disorders, including epilepsy, anxiety disorders, and schizophrenia.
How are amino acid transmitters distributed?
e.g. about 20% of CNS neurones are GABAergic
e.g. about 30% of all synapses are GABAergic
Glutamate mostly found in pyramidal neurones
GABA mostly found in short local interneurones
GABA also found in longer projection neurones
How is glutamate metabolised in the brain?
Glutamate in the CNS comes either from glucose (via Krebs cycle) or glutamine - synthesised by glial cells and taken up by neurones
Glutamate can be converted to GABA by the enzyme glutamic acid decarboxylase – GAD
Glutamate (Glu) is stored in synaptic vesicles and released by calcium-dependent exocytosis.
How is GABA metabolised in the brain?
GABA is released from presynaptic neurons and binds to GABA receptors on postsynaptic neurons.
After exerting its inhibitory effect, GABA is reabsorbed by neurons and glial cells.
Inside cells, GABA is primarily metabolized by GABA transaminase (GABA-T) to form succinic semialdehyde then succinate.
Succinate enters the Krebs cycle, where it is metabolized to produce energy.
In the brain, glutamate is generated as a byproduct, which is converted to glutamine and can be recycled back into the neurons, closing the glutamate-GABA-glutamine cycle.
What are ionotropic receptors?
Or ligand gated ion channels, transmembrane proteins that allow ions to pass through cell membranes.
What are metabotropic receptors?
Also G-protein-coupled receptors (GPCRs), are membrane receptors that regulate cell activity. They are involved in many neurotransmitter systems, hormone signaling, and second messenger systems
What are ionotropic gaba receptors?
Ligand-gated ion channel activated by GABA that lets through chloride
Mediates fast hyperpolarization and therefore inhibition
Multi-subunit receptors located throughout the brain
GABA a vs GABA b
GABAA: Ligand-gated ion channels that form chloride channels
GABAB: G protein-coupled receptors that modulate potassium and calcium channels
What are GABAb receptor agonists?
Spasticity can be viewed as an exaggerated activity of the stretch reflex pathways
For pain, muscle relaxation, sedation
e.g. Baclofen is used to treat spasticity
Crosses BBB so sedation is an issue
