Ligand-Gated Ion Channels: Structure, Function, and Pharmacology in Neurotransmission

What opens ligand-gated ion channels?

The binding of a ligand (e.g., acetylcholine, serotonin, glutamate).

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

To provide initial depolarization necessary to open voltage-gated channels.

How do ligand-gated ion channels differ from voltage-gated channels?

Ligand-gated channels require a ligand to open, while voltage-gated channels open in response to changes in membrane potential.

What are the major families of ligand-gated ion channels?

Excitatory and inhibitory ligand-gated ion channels.

What is the structure of nicotinic acetylcholine receptors (nAChRs)?

They consist of 5 subunits with 4 transmembrane segments.

Where are nAChRs primarily found?

At the neuromuscular junction, autonomic ganglia, and throughout the nervous system.

What ions can pass through nAChRs?

Na+, K+, and in some cases Ca++.

What is the effect of nAChR activation on neurons?

It has an excitatory, depolarizing effect.

What are some agonists of nAChRs?

Nicotine, varenicline, carbachol, and galantamine.

What are some antagonists of nAChRs?

Curare, pancuronium, and bupropion.

What role do acetylcholinesterases play in synaptic transmission?

They degrade ACh, terminating its action at the synapse.

What happens to the membrane potential when ACh binds to nAChRs?

It generates depolarization due to cation influx.

What is the reversal potential for nAChR channels?

Near 0 mV due to the non-selective nature of the channel.

How does the amplitude of the current change with holding voltage?

More hyperpolarized holding voltages result in larger currents.

What is the significance of the concentration-response curve for LGICs?

It shows how increasing concentrations of agonist lead to larger currents.

What are the states of ligand-gated ion channels influenced by?

The binding of ligands (agonists) to the receptor.

What is the difference between the closed and open states of LGICs?

The closed state (R) is unbound, while the open state (AR*) has ligands bound.

What is the role of agonist binding in LGICs?

It promotes the transition between closed and open states of the channel.

What is the effect of multiple ligand binding on some LGICs?

Some channels require 2 agonist molecules to bind for channel opening.

What is the role of conformational changes in LGIC function?

They allow the channel to open in response to ligand binding.

What determines the cation specificity of the nAChR?

Rings of high negative charge on the cytoplasmic side of the receptor.

What happens to the hydration shell of ions as they pass through nAChR?

The negative charges remove the hydration shell of the passing ions.

What is the driving force for current flow in LGICs?

The voltage across the membrane once the channel is opened.

What is the significance of the reversal potential in relation to action potentials?

It helps ensure that the membrane potential reaches threshold for firing an action potential.

How do small depolarizations contribute to reaching threshold?

They add up from many ion channels opening and closing in response to input from pre-synaptic terminals.

What is the role of the extracellular domain (ECD) in nAChRs?

It is involved in ligand binding.

What is the intracellular domain (ICD) of nAChRs responsible for?

It is involved in the signaling pathways after channel activation.

What are the main types of receptors in the Nicotinic Receptor Superfamily?

Nicotinic acetylcholine receptors (nAChRs), GABA receptors, Glycine receptors, and Serotonin receptor 5-HT3.

How many subunits make up a Cys-loop receptor channel?

Five subunits, forming a pentameric structure.

What is the role of the Cys-loop in Cys-loop receptors?

It participates in ligand binding.

What type of ion channels are GABAA and GABAC receptors?

Ligand-gated ion channels.

What is the effect of GABAB receptors?

They are G-protein coupled receptors.

What ions are GABA receptors selective for?

Chloride (Cl-) and bicarbonate (HCO3-).

What is the primary effect of GABA on neurons?

Inhibitory, hyperpolarizing effect due to Cl- entering the cell.

What are the subunits of GABA receptors?

α, β, γ, δ, π, ρ, ε.

What are some agonists of GABAA receptors?

GABA and muscimol.

Name a competitive antagonist of GABAA receptors.

Bicuculline or flumazenil.

What are positive allosteric modulators of GABAA receptors?

Benzodiazepines, non-benzodiazepines, barbiturates, anesthetics, and ethanol.

What is the role of neurosteroids in relation to GABAA receptors?

They act as allosteric modulators.

What happens to Cl- channels during development in neurons?

They can cause excitation due to higher intracellular Cl- concentration.

What is the function of synaptic GABA receptors?

They mediate phasic inhibition.

What is the function of extrasynaptic GABA receptors?

They mediate tonic inhibition.

What are glycine receptors selective for?

Chloride (Cl-) and bicarbonate (HCO3-).

What are some agonists of glycine receptors?

Glycine, β or L-alanine, taurine, L-serine, proline.

What is the effect of GABA and glycine on postsynaptic neurons?

They can produce inhibitory post-synaptic potentials (IPSPs).

What is unique about 5-HT3 serotonin receptors?

They are the only ion channel receptor for serotonin.

What ions can flow through 5-HT3 receptors?

Na+, K+, and Ca++.

What is the primary effect of 5-HT3 receptor activation?

Excitatory, depolarizing effect on neurons.

What are some antagonists of 5-HT3 receptors?

Ondansetron, granisetron, tropisetron.

What characterizes NMDA receptors?

They are Na+, K+, and Ca++ permeable and require glycine as a co-agonist.

What is the role of Mg++ in NMDA receptor activation?

Mg++ blocks the channel and requires depolarization to be removed.

What are AMPA receptors primarily permeable to?

Na+ and K+.

What is the effect of AMPA receptor activation?

Excitatory, depolarizing effect on neurons.

What is the role of P2X family receptors?

They are activated by ATP and are excitatory, depolarizing channels.

What do ASICs respond to?

They are activated by H+ and are involved in pain perception.

What is the significance of TRP channels?

They are involved in thermosensation and can be activated by temperature changes.

How can ion channels be modulated?

By lipids, G-proteins, and kinases.