Purinergic P2X and ASIC Ion Channels

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Questions and Answers

What type of receptor are P2Y receptors classified as?

Ion channels

Transient receptor potential channels

G-protein-coupled receptors (correct)

Ligand-gated ion channels

What is the structural composition of a P2X receptor?

A trimer of three subunits (correct)

A cluster of five subunits

Single subunit forming a dimer

A heptamer surrounding a channel

Which type of receptor is gated by ATP and is involved in mediating excitatory neurotransmission?

P2Y receptors

GABA receptors

P2X receptors (correct)

Serotonin receptors

What process typically releases ATP from cells prior to its conversion to ADP?

Exocytosis Signup and view all the answers

Which of the following receptor compositions is an example of hetero-oligomeric receptors?

P2X2:P2X3 in the nodose ganglion Signup and view all the answers

What is the structural composition of P2X receptors?

They are composed of three protein subunits. Signup and view all the answers

Which ions are P2X receptors primarily permeable to?

Na+, K+, and Ca2+ Signup and view all the answers

What types of oligomers can P2X receptors form?

Either homo-oligomeric or hetero-oligomeric Signup and view all the answers

Which kind of receptors are included alongside P2X receptors as ligand-gated ion channels?

Cys-loop receptors and ionotropic glutamate receptors Signup and view all the answers

How many P2X receptor subunits have been identified?

Seven Signup and view all the answers

What type of ions do ASICs primarily conduct?

Na+ Signup and view all the answers

Which of the following subunits are identified in ASICs?

ASIC1 Signup and view all the answers

What is the effect of amiloride on ASICs?

It blocks the channel. Signup and view all the answers

What is the primary physiological function of ASICs?

Modulate neuronal sensitivity to acidosis. Signup and view all the answers

Which body systems express ASICs?

Both the central and peripheral nervous systems (CNS and PNS). Signup and view all the answers

Which ASIC subunit has the highest pIC50 value for amiloride?

ASIC1a Signup and view all the answers

What does the term 'homo-oligomers' refer to in the context of ASICs?

Multiple identical ASIC subunits combined. Signup and view all the answers

In which cells have ASICs been detected?

In various cells, including taste receptor cells and lung epithelial cells. Signup and view all the answers

What is the primary mechanism of inhibition in the brain?

GABA-A receptors Signup and view all the answers

Which of the following substances are known as positive allosteric modulators for GABA-A receptors?

Benzodiazepines Signup and view all the answers

Which receptor is permeable to Cl- ions?

GABA-A receptors Signup and view all the answers

What role do 5-HT3 receptor antagonists like ondansetron play?

They are anti-emetics. Signup and view all the answers

Which ion is primarily permeable through 5-HT3 receptors?

Na+ Signup and view all the answers

Which drugs can evoke sedation at high doses by increasing GABA concentrations?

Barbiturates Signup and view all the answers

What characteristic of nAChRs is highlighted in the context of fast synaptic excitation?

They are permeable to cations. Signup and view all the answers

Which type of receptors are primarily involved in synaptic inhibition in the brain?

GABA-A receptors Signup and view all the answers

What physiological role do ionotropic glutamate receptors primarily serve in the CNS?

Fast synaptic excitation Signup and view all the answers

Which of the following ions are ionotropic glutamate receptors permeable to?

Na+, K+, and very permeable to Ca2+ Signup and view all the answers

What is a notable pharmacological characteristic of NMDA receptors?

They have open channel blockers such as ketamine. Signup and view all the answers

What potential consequence may arise from the over-activity of ionotropic glutamate receptors?

Cell death Signup and view all the answers

What defines the physiological distribution of P2X receptors?

Widespread in CNS, PNS, smooth muscle, and immune cells Signup and view all the answers

Which characteristic describes P2X receptors compared to ionotropic glutamate receptors?

Less understanding of their physiological roles. Signup and view all the answers

What is a key feature of AMPA and Kainate receptors?

They facilitate fast synaptic excitation. Signup and view all the answers

What is a common physiological function of the ionotropic glutamate receptor family?

Mediate synaptic transmission Signup and view all the answers

What structural characteristic defines P2X receptors?

They are trimers composed of three protein subunits. Signup and view all the answers

Which ion is exceptionally permeable through P2X receptors aside from Na+, K+, and Ca2+?

Cl- Signup and view all the answers

Which types of oligomers can P2X receptors form?

Homo-oligomeric and hetero-oligomeric Signup and view all the answers

What is a common physiological role of ionotropic glutamate receptors, which include P2X receptors?

Regulating neuronal excitability Signup and view all the answers

What challenge is often encountered in developing drugs that target P2X receptors?

Complex pharmacokinetics and selectivity Signup and view all the answers

Which physiological function is specifically associated with P2X1 receptors?

Urinary bladder contraction Signup and view all the answers

What is the effect of allosteric modulation on P2X receptors?

It alters their sensitivity to pH changes. Signup and view all the answers

Which P2X receptor is primarily involved with inflammatory responses in B cells?

P2X6 Signup and view all the answers

What role do P2X receptors play in the central nervous system?

Neuroinflammation Signup and view all the answers

What is the primary role of ATP in the context of P2X receptors?

It gates P2X receptors and mediates excitatory neurotransmission. Signup and view all the answers

Which structural characteristic is observed in P2X receptors?

They are trimeric receptors with three subunits surrounding an ion channel. Signup and view all the answers

Which agonist is selective for P2X receptors?

BzATP Signup and view all the answers

What type of oligomeric composition can P2X receptors exhibit?

Both homo-oligomeric and hetero-oligomeric compositions are possible. Signup and view all the answers

What is the significance of P2Y receptors in relation to ATP?

They interact with ADP after ATP is converted. Signup and view all the answers

What mechanisms facilitate the release of ATP from cells during damage?

Vesicular exocytosis of ATP from damaged cells. Signup and view all the answers

Which of the following cells are known to express acid-sensing ion channels (ASICs)?

Taste receptor cells Signup and view all the answers

What is the primary ion conducted by ASICs?

Sodium (Na+) Signup and view all the answers

What effect does amiloride have on ASICs?

Blocks ion conduction Signup and view all the answers

Which subunit of ASICs has the lowest pIC50 value for amiloride?

ASIC3 Signup and view all the answers

How do ASICs respond to increasing concentrations of H+?

Exhibit initial desensitization followed by activation Signup and view all the answers

Which of the following is NOT a physiological function of ASICs?

Stimulates smooth muscle contraction Signup and view all the answers

Which receptor family includes acid-sensing ion channels?

Epithelial Na+ channels (ENaC) Signup and view all the answers

What type of channel are ASICs classified as?

Ligand-gated channel Signup and view all the answers

What is the primary mechanism of inhibition in the brain related to GABA-A receptors?

Chloride influx Signup and view all the answers

Which of the following drugs are classified as positive allosteric modulators of GABA-A receptors?

Diazepam Signup and view all the answers

Which receptors are primarily involved in fast synaptic excitation?

nAChRs Signup and view all the answers

What physiological effect do 5-HT3 receptor antagonists like ondansetron primarily have?

Act as anti-emetics Signup and view all the answers

Which of the following ions can pass through GABA-A receptors?

Chloride ions Signup and view all the answers

Which of the following drug classes is involved in enhancing GABA activity in the central nervous system?

Benzodiazepines Signup and view all the answers

In which body systems are 5-HT3 receptors predominantly found?

Central nervous system and enteric nervous system Signup and view all the answers

Which of the following best describes the permeability profile of 5-HT3 receptors?

Non-selective for cations, including Na+ and Ca2+ Signup and view all the answers

Study Notes

Purinergic P2X Receptors

P2X receptors are a family of ligand-gated ion channels that are activated by adenosine triphosphate (ATP).
They are trimeric, meaning they are composed of three protein subunits.
They are permeable to sodium, potassium, and calcium ions.
They can be either homo-oligomeric (composed of the same subunits) or hetero-oligomeric (composed of different subunits).
There are seven identified subunits, P2X1-7.

Acid-Sensing Ion Channels (ASICs)

ASICs are also trimeric ligand-gated ion channels.
They are activated by H+ (protons), which is released from the cell in various conditions, including ischemia, inflammation, and acidosis.
They are permeable to sodium.
There are three identified subunits: ASIC1, ASIC2, and ASIC3.
ASICs are expressed in both the central nervous system (CNS) and the peripheral nervous system (PNS), where they modulate neuronal sensitivity to acidosis and play a role in a variety of processes, including pain, taste, and hearing.
They are blocked by amiloride.
ASICs share a common ancestor with epithelial sodium channels (ENaCs), which are constitutively active (always on).

ASIC Pharmacology

The potency of H+ (pEC₅₀) for ASICs varies depending on the subunit composition:
- ASIC1a: pEC₅₀ = 6.2 - 6.8
- ASIC2: pEC₅₀ = 4.1 - 5.0
- ASIC3: pEC₅₀ = 6.2 - 6.7
ASICs are inhibited by amiloride, the potency of which also varies with the subunit composition:
- ASIC1a: pIC₅₀ = 5.0
- ASIC2: pIC₅₀ = 4.6
- ASIC3: pIC₅₀ = 4.2 - 4.8

### Summary of Ligand-Gated Ion Channels (LGICs)

Cys-loop receptors
- Nicotinic acetylcholine receptors: expressed throughout the CNS and PNS, mediate rapid excitatory synaptic transmission, including at the neuromuscular junction. These receptors are permeable to sodium, potassium, and calcium ions, and are blocked by drugs like curare.
- 5-HT3 receptors: expressed in the CNS, PNS, and enteric nervous system, are permeable to sodium, potassium, and calcium ions, and mediate excitatory synaptic transmission.
- GABA-A receptors: primarily expressed in the CNS, mediate rapid inhibitory synaptic transmission, and are permeable to chloride. They are targeted by many drugs used to treat anxiety, insomnia, seizures, and pain, including benzodiazepines, barbiturates, and general anaesthetics.
Ionotropic glutamate receptors
- NMDA receptors: expressed in the CNS, primarily in the limbic regions of the brain, mediate rapid excitatory synaptic transmission, and are permeable to sodium, potassium, and particularly calcium ions. They are involved in learning and memory.
- AMPA receptors: expressed in the CNS, particularly the limbic regions of the brain, mediate rapid excitatory synaptic transmission, and are permeable to sodium, potassium, and calcium ions.
- Kainate receptors: expressed in the CNS, particularly the limbic regions of the brain, mediate rapid excitatory synaptic transmission, and are permeable to sodium, potassium, and calcium ions. They are involved in learning and memory.
P2X receptors: expressed throughout the body, including the CNS, PNS, and smooth muscle, and mediate rapid excitatory synaptic transmission upon binding the neurotransmitter ATP.
- P2X receptors are permeable to sodium, potassium, and calcium ions.
ASICs: expressed throughout the body, including the CNS and PNS, mediate rapid excitatory synaptic transmission upon binding H+ (protons).
- They are permeable to sodium ions.

Ligand-Gated Ion Channel Receptors

Cys-loop receptors include nicotinic acetylcholine receptors, 5-HT3 receptors, GABA-A receptors, the strychnine-sensitive glycine receptor, and the zinc-activated channel (ZAC)
Ionotropic glutamate receptors include NMDA receptors, AMPA receptors and kainate receptors

P2X receptors

P2X receptors are trimers, which means they’re composed of three protein subunits.
The P2X receptors are permeable to sodium, potassium, and calcium ions, but not chloride (exceptionally).
Like Cys-loop receptors and ionotropic glutamate receptors, P2X receptors can be either homo-oligomeric (composed of the same subunit) or hetero-oligomeric (composed of different subunits).
There are seven subunits identified (P2X1-7).
There are also P2Y receptors that are G-protein-coupled receptors.

P2X receptor structure

Each subunit has two transmembrane domains that contribute to the pore of the ion channel.
The receptor is a trimer, with three subunits, around a centrally located ion channel.

P2X receptor function

They’re gated by ATP and mediate excitatory neurotransmission in the CNS and smooth muscle.
They’re expressed in a variety of tissues, including the nervous system, smooth muscle, and skeletal muscle.

P2X receptor pharmacology

P2X receptors are agonists for ATP, selective agonists include αβ-me-ATP and BzATP.
Antagonists include suramin (an anti-parasitic drug) at P2X1, P2X2, P2X3, and P2X5 receptors.
P2X receptors are involved in synaptic transmission, cardiac function, excitation in the gut, kidney function, vascular tone, and nociception.
They are also involved with apoptosis and inflammatory responses.
P2X receptors are allosterically modulated by changes in pH.

Examples of P2X receptors and their function

P2X1 in smooth muscle and the urinary bladder is associated with contraction.
P2X2, P2X3, and P2X2/3 in the nervous system, sensory neurons, are associated with taste perception.
P2X4 in the CNS is associated with neuroinflammation.
P2X5 in B cells and T cells is associated with inflammation and chloride conductance.
P2X6 in B cells is generally associated with a pro-inflammatory immune response.
P2X7 in the heart, liver, skeletal muscle, pancreas, thymus, tonsils, monocytes, macrophages, and osteoclasts is associated with inflammation.

Acid-sensing (H+-gated) ion channels (ASICs)

ASICs are trimers that conduct sodium.
There have been three subunits identified: ASIC1, ASIC2, and ASIC3.
They are activated by H+ and blocked by amiloride.
They are expressed in the CNS and PNS to modulate neuronal sensitivity to acidosis.
ASICs have been detected in taste receptor cells, photoreceptors, lung epithelial cells, urothelial cells, adipose cells vascular smooth muscle cells), immune cells, and bone.
They’re related to epithelial sodium channels (ENaC) which are not ligand-gated but constitutively active.

The structure of ASICs

ASIC1a homo-oligomers initially desensitize followed by activation with increasing H+ concentration.
The subunit ASIC1a has a H+ pEC50 of 6.2-6.8, and an amiloride pIC50 of 5.0.
The subunit ASIC2 has a H+ pEC50 of 4.1-5.0, and an amiloride pIC50 of 4.6.
The subunit ASIC3 has a H+ pEC50 of 6.2-6.7, and an amiloride pIC50 of 4.2-4.8.

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Description

This quiz explores the characteristics and functions of Purinergic P2X receptors and Acid-Sensing Ion Channels (ASICs). Learn about their structure, activation mechanisms, and the role they play in physiological processes. Ideal for students studying neurobiology or cellular physiology.