Structure and Function of P2X Receptors and ASICs

P2X Receptors

Ion channels gated by ATP, involved in various tissues.

Acid-Sensing Ion Channels

Ion channels activated by H+, important for pain and taste.

Selective Ligands

Compounds that specifically bind to P2X receptors.

Hetero-Oligomers

Receptors composed of different subunits, e.g., P2X2/3.

ATP

Adenosine triphosphate, primary agonist for P2X receptors.

AB-methylated ATP

Selective ligand for P2X, no affinity for P2Y.

Transgenic Knockout Studies

Research method to assess physiological functions of receptors.

Patch Clamp Electrophysiology

Technique to measure ionic currents in cells.

Subunit Composition

Determines receptor properties and ligand selectivity.

Vesicular Release

Release of ATP from damaged cells, triggers responses.

P2X4 Receptors

Subtype expressed in various tissues, lacks selective ligands.

P2X7 Receptors

Subtype involved in inflammation, expressed in immune cells.

Pharmacological Challenges

Difficulties in developing drugs due to receptor diversity.

Gated by ATP

P2X receptors require ATP binding for activation.

Extracellular Ion Flow

Facilitates ion movement upon receptor activation.

Nervous System Expression

P2X receptors present in sensory neurons and ganglia.

pH Modulation

Local pH changes can affect ion channel conductance.

P2Y Receptors

G protein-coupled receptors also activated by ATP.

Neurotransmitter Release

P2X receptors facilitate release in synaptic transmission.

Enteric Nervous System

Regulates gut motility, involves P2X receptors.

ASICs

Acid-sensing ion channels, detect H+ concentration changes.

Amiloride

Antagonist of epithelial Na+ channels, affects blood pressure.

Physiological Functions

Roles of P2X receptors in bladder contraction and inflammation.

Subunit Homology

P2X subunits share about 40% similarity, complicating drug design.

Pain Perception

Acid-sensing channels are crucial for sensing pain.

Taste Perception

Changes in pH detected by acid-sensing channels influence taste.

Homo-Oligomers

Receptors composed of identical subunits, e.g., P2X1.

Ion Channel Structure

Trimers with complex extracellular regions and transmembrane domains.

Cation Channels

Channels primarily allowing Na+, K+, and Ca2+ ions.