Neuronal Signalling in CNS Disorders Flashcards

Vocabulary flashcards covering core concepts of neuronal signalling, transmembrane transport, action potentials, neurotransmitters, and associated CNS disorders from the lecture notes.

Electrochemical gradient

A driving force for transmembrane transport, generated by active transport mechanisms (pumps, ATP-ases), composed of a chemical driving force (concentration gradient) and an electrical driving force (charge difference).

Chemical driving force

The concentration gradient across the membrane, one component of the electrochemical gradient.

Electrical driving force

The charge difference across the membrane, one component of the electrochemical gradient.

Membrane potential (Vm)

A voltage difference across the plasma membrane, representing the sum of equilibrium potentials (Eion) of all contributing ions.

Equilibrium potential (Eion)

The membrane potential at which the electrical and chemical forces for a specific ion are balanced, resulting in no net movement of that ion across the membrane.

Goldman-Hodgkin-Katz Equation

A mathematical equation used to calculate the membrane potential, taking into account the permeability and concentrations of multiple ions (K+, Na+, Ca2+, Cl-) across the cell membrane.

Simple diffusion

The free movement of molecules or ions from a region of high concentration to a region of low concentration, without the help of carriers.

Facilitated diffusion

Diffusion that is helped by transmembrane carriers and ion channels (integral transmembrane proteins forming pores for ions).

Primary active transport

Movement of ions from a region of low concentration to a region of high concentration, conducted by ion pumps that directly use the energy of ATP.

Secondary active transport

Movement of ions that uses the free energy of an electrochemical gradient for one component to transport another component against its chemical gradient, not directly hydrolyzing ATP.

Passive transport

Transmembrane transport that occurs downhill, releasing energy by moving molecules down their concentration or electrochemical gradient.

Active transport

Transmembrane transport that occurs uphill, consuming energy to move molecules against their concentration or electrochemical gradient.

Voltage-gated ion channels

Transmembrane proteins that form ion channels activated by changes in the electrical membrane potential, typically ion-specific (e.g., to Na+, K+, Ca2+, Cl- ions).

What is the primary function of voltage-gated ion channels?

They are protein pores in the cell membrane that allow facilitated diffusion of specific ions (like K+, Na+, Ca2+) across the membrane, moving ions down their concentration gradient.

What does the "voltage-gated" part mean?

The channels open or close in response to a change in the electrical potential (voltage) across the cell membrane.

What structure is responsible for sensing the change in membrane potential?

The Voltage Sensor (a segment of the channel protein).

Which type of amino acids typically represent the voltage sensor, and why?

Positively charged amino acids, such as Arginine and Lysine. Their charge makes them sensitive to the surrounding electric field

What happens to the channel when the membrane is at a negative resting potential (e.g.,

−70mV)?

The channel is usually CLOSED, and ion conduction is minimal.

What process causes the channel to open?

Depolarization (when the membrane potential becomes less negative, e.g.,

−70mV to-40 mV), which shifts the voltage sensor, changing the channel's conformation.

Give two examples of factors, besides voltage, that can regulate some ion channels.

Internal Calcium Concentration (for calcium-sensitive K+ channels) and Phospholipids inside the cell.

Are these channels highly specific?

Yes. Voltage-gated channels are generally quite selective, meaning a potassium channel will predominantly conduct K+ ions, and a sodium channel will primarily conduct Na+ ions.

Ligand-gated ion channels (LICs)

Membrane proteins that open in response to the binding of a neurotransmitter, hormone, or drug, typically nonselective and allowing Na+, K+, Ca2+, and/or Cl- to pass.

Ionotropic receptors

Another name for ligand-gated ion channels, as they directly form an ion channel.

G-protein coupled receptors (GPCRs)

Receptors that detect molecules outside the cell and activate internal signal transduction pathways through G proteins, rather than directly forming an ion channel or carrier.

Metabotropic receptors

Another name for G-protein coupled receptors, due to their metabolic signaling cascade rather than direct ion channel activity.

Na+/K+-ATPase

A primary active transport pump that uses ATP to move 3 Na+ ions out of the cell and 2 K+ ions into the cell, maintainingresting membrane potential.

Na+/Ca2+ - exchanger (NCX)

A secondary active transport pump that uses the electrochemical gradient of Na+ to export Ca2+ from the cell.

Depolarization

A reduction of the charge difference between the inside and outside of the cell (Vm < -70mV), typically due to increased influx of Na+ and/or Ca2+, leading to increased neuronal excitability.

Hyperpolarization

An increase of the charge difference between the inside and outside of the cell (Vm > -70mV), primarily due to increased efflux of K+, leading to decreased neuronal excitability.

Resting membrane potential

The stable, negative voltage difference across the plasma membrane of an excitable cell when it is not actively transmitting electrical signals, typically around -70 mV.

Action potential

A rapid, transient change in voltage that occurs between the inside and outside of an excitable cell (neuron or muscle) spontaneously or as a result of stimulation.

Overshoot (Action potential)

The phase of the action potential where the membrane potential becomes positive (above 0 mV) during depolarization.

Afterhyperpolarization (Action potential)

A phase following repolarization where the membrane potential briefly becomes more negative than the resting membrane potential.

Amplitude (Spike height)

The total vertical height of an action potential spike, calculated as the sum of overshoot and afterhyperpolarization.

Voltage-gated sodium channel (Nav)

Ion channels responsible for the fast depolarization phase (Phase 1) of an action potential by allowing rapid influx of Na+ ions into the cell.

Voltage-gated potassium channel (Kv)

Ion channels responsible for the repolarization (Phase 2) and afterhyperpolarization (Phase 3) phases of an action potential by allowing efflux of K+ ions out of the cell.

Hyperpolarization and Cyclic Nucleotide (HCN) sensitive channels

Channels contributing to the slow depolarization during resting membrane potential (Phase 0 and 4) through a leak Na+ current, important for pacemaking activity.

Phase 0 (Action Potential)

The resting membrane potential and slow depolarization phase, driven by HCN channels.

Phase 1 (Action Potential)

The fast depolarization phase, primarily due to the rapid influx of Na+ through voltage-gated sodium channels.

Phase 2 (Action Potential)

The repolarization phase, primarily due to the efflux of K+ through voltage-gated potassium channels.

Phase 3 (Action Potential)

The afterhyperpolarization phase, where the membrane potential becomes maximally polarized and more negative than resting, due to sustained K+ efflux.

Phase 4 (Action Potential)

The return to resting membrane potential and initiation of slow depolarization for the next action potential, also driven by HCN channels and Na+/K+-ATPase.

Acetylcholine (ACh)

A neurotransmitter that is mostly excitatory, acting on nicotinic and muscarinic receptors and influencing Na+ and Ca2+ currents.

Glutamate

A major excitatory neurotransmitter in the CNS, acting on NMDA and AMPA receptors primarily to cause Na+ and Ca2+ influx and depolarization (EPSPs).

GABA (Gamma-aminobutyric acid)

A major inhibitory neurotransmitter in the CNS, acting on GABAA (Cl- current) and GABAB (K+-inhibitory) receptors to cause hyperpolarization (IPSPs).

Glycine

An inhibitory neurotransmitter, acting on GLRα1-4 + GLRβ receptors and primarily influencing Cl- currents.

Noradrenaline (Norepinephrine)

An excitatory neurotransmitter, synthesized in the adrenal medulla and sympathetic neurons, acting on α and β receptors and influencing Na+ and Ca2+ currents.

Dopamine

An excitatory neurotransmitter, synthesized in specific brain regions, acting on D1-5 receptors and influencing Na+ and Ca2+ currents.

Serotonin (5-HT)

A neurotransmitter produced in the midbrain and hypothalamus; can be inhibitory or excitatory, acting on 5-HT1-7 receptors and influencing Na+ and Ca2+ currents.

Histamine

A neurotransmitter that can be inhibitory or excitatory, acting on H1-4 receptors and influencing Na+ and Ca2+ currents.

ATP (Neurotransmitter)

A neurotransmitter that can be inhibitory or excitatory, acting on P2X and P2Y receptors and influencing Na+ and Ca2+ currents.

Depression

A mood disorder associated with reduced levels of noradrenaline and serotonin, characterized by poor memory, lack of energy/motivation, and mood disturbances.

Parkinson's disease (PD)

A neurodegenerative disorder characterized by the degeneration of dopamine neurons in the substantia nigra pars compacta, leading to tremors, slow movement (bradykinesia), and muscle rigidity. Also associated with low acetylcholine.

Attention-Deficit Hyperactivity Disorder (ADHD)

A disorder associated with reduced dopamine levels, characterized by difficulties with attention, hyperactivity, and impulsivity.

Schizophrenia

A psychiatric disorder historically linked to abnormally high levels of D2 dopamine receptor expression (dopamine hypothesis), also linked to excessive glutamate release.

Serotonin syndrome

A potentially life-threatening condition caused by excessive serotonin levels, leading to symptoms like confusion, agitation, headache, increased blood pressure/temperature, tremor, and seizures.

Acetylcholinesterase (AChE)

An enzyme that breaks down acetylcholine in the synaptic cleft, and its inhibition leads to increased ACh levels.

Alzheimer’s Disease (AD)

A progressive neurological disorder and common cause of senile dementia, characterized by memory loss and other intellectual deficits, strongly associated with a cholinergic deficit.

Myasthenia gravis

An autoimmune condition associated with low levels of acetylcholine, causing muscle weakness, drooping eyelids, blurred vision, and difficulty swallowing/speaking.

Donepezil

A reversible selective inhibitor of acetylcholinesterase (AChE), approved for the symptomatic treatment of Alzheimer's disease to compensate for acetylcholine deficiency.

Excitatory Post-Synaptic Potentials (EPSPs)

Depolarizations of the postsynaptic membrane caused by excitatory neurotransmitters like glutamate, increasing the likelihood of an action potential.

Inhibitory Post-Synaptic Potentials (IPSPs)

Hyperpolarizations of the postsynaptic membrane caused by inhibitory neurotransmitters like GABA, decreasing the likelihood of an action potential.

Temporal lobe epilepsy (TLE)

A neurological disorder associated with decreased GABA activity and excessive glutamate release.

Huntington's disease (HD)

A neurodegenerative disorder associated with decreased GABA activity and excessive glutamate release.

"What are the two major driving forces that determine ion movement across the plasma membrane?"

"Chemical (concentration) gradient and electrical gradient."

"What is the electrochemical gradient?"

"The combined effect of the chemical (concentration) gradient and electrical gradient on ion movement."

"Why is the inside of the cell more negative than the outside?"

"Because of large negatively charged organic anions (e.g. proteins nucleic acids) that cannot cross the membrane."

"What determines the resting membrane potential?"

"The electrochemical gradients of ions especially K⁺ across the plasma membrane."

"Which enzyme maintains the electrochemical gradient across the plasma membrane?"

"The Na⁺/K⁺-ATPase pump."

"How many Na⁺ and K⁺ ions are transported by the Na⁺/K⁺ pump and in which directions?"

3 Na⁺ are pumped out, 2 K⁺ are pumped in."

"What provides the energy for the Na⁺/K⁺-ATPase pump?"

"Hydrolysis of ATP to ADP + Pi."

"Is ion movement through the Na⁺/K⁺-ATPase pump passive or active transport?"

"Active transport (ions move against their electrochemical gradients)."

"What is the typical intracellular concentration of potassium (K⁺) in excitable cells?"

"~140 mM dominant cation inside the cell."

"What is the typical extracellular concentration of potassium (K⁺)?"

"~5 mM maintained by Na⁺/K⁺-ATPase pump."

"What happens if extracellular potassium rises (hyperkalemia)?"

"Resting membrane potential becomes less negative can cause pathological effects often kidney-related."

"What is the typical intracellular concentration of sodium (Na⁺)?"

"~10–15 mM."

"What is the typical extracellular concentration of sodium (Na⁺)?"

"~145 mM dominant cation in extracellular fluid."

"What is the main role of sodium and chloride in the body?"

"Maintaining osmolarity and contributing to depolarization during action potentials."

"What is the typical intracellular concentration of calcium (Ca²⁺) at rest?"

"~0.1 µM (very low)."

"What is the typical extracellular concentration of calcium (Ca²⁺)?"

"~1.2 mM (high) creating a steep gradient."

"What are the roles of calcium in cells?"

"Depolarization second messenger: muscle contraction synaptic transmission protein synthesis apoptosis."

"What is the typical intracellular concentration of chloride (Cl⁻)?"

"Lower than extracellular varies by cell type."

"What is the typical extracellular concentration of chloride (Cl⁻)?"

"~110–120 mM similar to sodium."

"What mainly determines the negative charge of the cytoplasm?"

"Impermeant anions such as proteins phosphates carbonates."

"What determines the resting membrane potential?"

"Equilibrium potentials of all major ions (K⁺ Na⁺Ca²⁺, Cl⁻) combined."

"Which ion primarily drives the resting membrane potential?"

"Potassium (K⁺) but influenced by all ions."

"What is the primary trigger for opening a ligand-gated ion channel (Ionotropic Receptor)?"

"The binding of a specific molecule called a **ligand** (e.g. a neurotransmitter) to an extracellular binding site on the channel protein."

"How does the mechanism of a ligand-gated channel differ from a voltage-gated channel?"

"**Voltage-gated** channels open due to changes in membrane **voltage**; **Ligand-gated** channels open due to **chemical binding**."

"What is a common example of a ligand-gated ion channel mentioned?"

"The **Nicotinic Acetylcholine Receptor** (nAChR)."

"What happens when Acetylcholine binds to the nicotinic receptor?"

"The channel opens allowing **sodium (Na+)** to rush into the cytoplasm which **depolarizes** the cell and makes it more excitable."

"Where is the nicotinic receptor important for its role in depolarization?"

"The **Parasympathetic Nervous System** (and neuromuscular junctions)."

"Compared to voltage-gated channels how specific are ligand-gated ion channels?"

"They are **not very specific**. They often conduct a wide range of **cations** (positively charged ions) in general such as sodium and calcium."

"What is another name for ligand-gated ion channels used to distinguish them from G-protein coupled receptors?"

"**Ionotropic Receptors**."

"Name another common example of a ligand-gated receptor mentioned."

"The **NMDA** (N-methyl-D-aspartate) receptor."

"What is the alternate name for a Metabotropic Receptor?"

"**G-protein Coupled Receptor (GPCR)**."

"Are Metabotropic Receptors ion channels themselves?"

"**No.** They are not channels; they regulate the activity of separate ion channels."

"Why are they called G-protein coupled receptors?"

"Because they are physically coupled to **G-proteins** (a type of membrane protein)."

"What do G-proteins bind to giving them their name?"

They bind to Guanosine Triphosphate (GTP), similar to how other proteins bind to ATP."

"What happens immediately after a ligand (e.g. adrenaline) binds to a GPCR?"

"The receptor transmits a conformational change to the G-protein causing the G-protein to **dissociate** (split into its alpha subunit and beta-gamma subunit)."

"What does the dissociated G-protein subunit do next?"

"It binds to an **effector protein** (e.g. adenylyl cyclase phospholipase C) which then acts on downstream targets."