Neurotransmitters in Characean Electrical Signaling
Akula Ramakrishna, Victoria V. Roshchina in Neurotransmitters in Plants, 2018
Coleman found a hyperpolarization-dependent Cl− channel in C. australis plasma membrane (Coleman 1986). Ca2+-dependent Cl−-permeable channel was found. The anion channel was activated by Ca2+on the cytoplasmic side, and its opening was voltage dependent. The authors supposed that the anion channel is concerned with generation of action potentials at the plasma membrane (Okihara et al. 1991). The channel activity was inhibited by calmodulin antagonists. In addition, Okihara et al. (1993) demonstrated that activity of the Ca2+-dependent Cl−-permeable channel is regulated by calmodulin applied to the cytoplasmic side of the inside-out patch-clamp recording. The activity of the channel, which had been enhanced by Ca2+, became low during the recording. However, the decrease of the activity could be stopped by applying calmodulin.
Benzodiazepines, Benzodiazepine Receptors, and Endogenous Ligands
Siegfried Kasper, Johan A. den Boer, J. M. Ad Sitsen in Handbook of Depression and Anxiety, 2003
GABA is the major inhibitory transmitter in the central nervous system. It is estimated that about 30% of all synapses of the brain use GABA as a transmitter [14]. Most of the physiological actions of GABA are mediated by GABAA receptors. These receptors are composed of five protein subunits forming a central chloride ion channel that can be opened by GABA (Fig. 2). So far, at least 6α, 3β, 3γ, 1δ, 1ε, 1π, 1θ, and 3ρ subunits have been identified in the mammalian nervous system [18] and, depending on their subunit composition, receptors exhibit distinct pharmacological and electrophysiological properties [14]. Recent immunocytochemical studies have indicated that individual subunits exhibit a distinct and often widespread distribution throughout the nervous system [24,25]. The resulting expression of multiple subunits in the same neurons suggest the existence of a large variety of GABAA-receptor subtypes in the brain.
Neurotransmitters and pharmacology
Mark J. Ashley, David A. Hovda in Traumatic Brain Injury, 2017
Two subtypes of GABA receptor have been described in detail and are referred to as GABAA and GABAB receptors. The GABAA receptor has been more thoroughly investigated and is a ligand-gated ion channel that functions as a channel for the chloride ion.136,147,148 This receptor is usually placed in a gene superfamily that also includes the nicotinic acetylcholine receptor, 5-HT3 receptor, and the glycine receptor. This gene superfamily is sometimes called the cys-loop family, which distinguishes it from the excitatory amino acid ligand-gated channel family of receptors.136 GABAA receptors are stimulated by GABA, muscimol, and isoguvacine and are blocked by the convulsants bicuculline (competitive antagonist) and picrotoxin (noncompetitive antagonist). The GABAA receptor is a heteropentamer composed of five polypeptide subunits forming the chloride ion channel in the cell membrane. The GABAA receptor contains several distinct binding sites for different chemicals that can modulate its function (see the following).
Mechano-gated channels in C. elegans
Published in Journal of Neurogenetics, 2020
Mechano-gated channels are evolutionarily conserved mechanical gates regulating mechanosensation like touch, hearing and proprioception (Kung, 2005). Through mechanotransduction process, gated ion channels convert mechanical stimuli into electrochemical signals thereby triggering mechanosensation. When a mechanical stimulus is applied, membrane tension or force spring leads to structural deformation of the gated protein. As such, the gated channel opens in order to allow the flow of ions to generate graded receptor potentials which triggers mechanosensation (Marshall & Lumpkin, 2012). Bacterial mechanosensitive channels (MscL, MscS and MscM) in E.coli are gated by changes of membrane tension forming non-selective pores through which hydrated ions and solutes can flow, and act as osmosensors for turgor control (Rasmussen & Rasmussen, 2018). In eukaryotes, a few cation-selective channels — degenerin and epithelial sodium channels (DEG/ENaC), N-type Transient receptor potential (TRPN), two-pore potassium channels (K2P), transmembrane-like proteins (TMC) and Piezo have been classified as bona fide mechano-gated channels (Delmas & Coste, 2013; Jin, Jan, & Jan, 2020). It is still enigmatic whether any anion channel such as chlorides can characterize mechano-gated channels.
ELX-02: an investigational read-through agent for the treatment of nonsense mutation-related genetic disease
Published in Expert Opinion on Investigational Drugs, 2020
CF is a prevalent, monogenic, hereditary, life-shortening disorder with nearly 10% of the patient population bearing an allele carrying a nonsense mutation [5]. From a phenotypic standpoint, CF is a chronic, progressive, multisystem disease of secretory glands, causing severe damage primarily in the lungs and digestive systems. The disease characteristics include salty-tasting skin, poor growth, poor weight gain despite normal food intake, frequent chest infections, and coughing or shortness of breath [5,6,7–8]. CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that result in disease-causative alleles which are hereditary in transmission in an autosomal recessive pattern [9,10]. The CFTR protein functions as an adenosine triphosphate-gated anion channel that primarily transports chloride and bicarbonate ions according to their electrochemical gradients [11]. Disease severity and rate of progression in CF correlates with the amount of CFTR activity in the apical membrane of the respiratory epithelia cells [12]. Nonsense mutations generally yield no functional CFTR, and individuals carrying these alleles are typically among those with the most severe form of disease [12]. Despite great progress in the clinical availability of CFTR-directed small molecules that improve protein trafficking or channel potentiation, these CFTR protein-directed therapies are ineffective against CFTR nonsense alleles.
The relevant targets of anti-oxidative stress: a review
Published in Journal of Drug Targeting, 2021
Transient receptor potential(TRP)channels are non-selective cation channels across cell membranes. In 1969, Cosens and Manning discovered for the first time that the Trp channel could generate transient rather than continuous spike potential under continuous light stimulation in drosophila with Trp gene mutation [104], hence the name Trp channel. The TRPC channel is one of the important members of the TRP family. It consists of six transmembrane domains (TMs), and the ion channel pore is located between TM5 and TM6. TRPC channels include seven different subtypes, namely TRPC1-7. Except TRPC2, the other six subtypes are widely expressed in a variety of human tissues and cells including cardiomyocytes. In myocardial tissue, TRPC1, TRPC3, TRPC 4 and TRPC 6 are distributed in the mouse sinoatrial node area and pacemaker cells, and TRPC3 and TRPC6 are also expressed in extranodal tissues [105,106].