Interplay between Gating and Block of Ligand-Gated Ion Channels

Abstract

Drugs that inhibit ion channel function by binding in the channel and preventing current flow, known as channel blockers, can be used as powerful tools for analysis of channel properties. Channel blockers are used to probe both the sophisticated structure and basic biophysical properties of ion channels. Gating, the mechanism that controls the opening and closing of ion channels, can be profoundly influenced by channel blocking drugs. Channel block and gating are reciprocally connected; gating controls access of channel blockers to their binding sites, and channel-blocking drugs can have profound and diverse effects on the rates of gating transitions and on the stability of channel open and closed states. This review synthesizes knowledge of the inherent intertwining of block and gating of excitatory ligand-gated ion channels, with a focus on the utility of channel blockers as analytic probes of ionotropic glutamate receptor channel function.

Recent breakthroughs and future directions in drugging aquaporins

“…Ubiquitous modulation by divalent cations is a theme seen across many types of ion channels and receptors, including N-methyl-D-aspartate (NMDA) glutamate receptors, cation channels, K + channels, Na + channels, and others as reviewed previously [68]. Tyrosine phosphorylation in the C-terminal domain increased the activation of AQP1 by cGMP [69].…”

Into the Tissues: Extracellular Matrix and Its Artificial Substitutes: Cell Signalling Mechanisms

“…Ion channels are permeable (mainly, but not exclusively) to ions of a given type, e.g., sodium ions [ 333 , 334 , 335 , 336 , 337 ]. The function of channels can be stopped by binding of so-called blockers [ 338 ]. In addition to ligand-gated ion channels, there are also voltage-gated ion channels (activated by changes in electrical membrane potential) and stretch-activated ion channels (responding to membrane stress) [ 339 , 340 , 341 ].…”

Bibliometric analysis of nicotinic acetylcholine receptors channel research (2000-2020)

“…The structure of nAChR subunits is composed of a large extracellular N-terminal domain (NTD; the location of the Cys-loop), three hydrophobic transmembrane regions (M1-M3), a variable intracellular loop, a fourth transmembrane region (M4), and a short extracellular C-terminus. The M1, M3, andM4 segments separate the pore-lining region from the hydrophobic membrane [ 2 , 33 , 34 ].…”

“…There are two types of acetylcholine receptors (AChR): nicotinic AChR (nAChR) and muscarinic AChR. nAChRs are fast cationic channels, initially discovered in muscles and autonomic ganglia function, while muscarinic AChRs are class I heptahelical G-protein-coupled receptors with a slower signaling pace [ 1 , 2 ].…”