High pH accelerates GABA deactivation on perch-rho1B receptors
1Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 West Taylor Street, Chicago, IL 60612, USA. hqian@uic.edu
Neuroscience
|August 22, 2006
Summary
High pH uniquely affects perch-rho(1B) GABA-C receptors, accelerating GABA deactivation and reducing sensitivity. This suggests alkalization lowers the receptor's gating efficiency, with key residues in the N-terminal region.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Ionotropic GABA(C) receptors, composed of GABA rho subunits, are modulated by pH.
- Perch retina GABA rho subunits' proton sensitivity is not fully understood.
Purpose of the Study:
- Investigate the proton sensitivity of perch retina GABA rho subunits.
- Characterize the novel effect of high pH on the perch-rho(1B) homomeric receptor.
Main Methods:
- Oocyte expression system
- Electrophysiology to measure GABA-elicited currents
- Construction and analysis of chimeric receptors
Main Results:
- High extracellular pH (9.5) accelerated GABA deactivation and reduced GABA sensitivity for perch-rho(1B) receptors.
- Acidification affected all examined GABA rho receptors, but high pH effects were specific to perch-rho(1B).
- High pH reduced maximum response amplitude for partial agonists (I4AA, beta-alanine), indicating reduced gating efficiency.
- Alkaline-sensitive residues were localized to the N-terminal region of perch-rho(1B).
Conclusions:
- External alkalization reduces the gating efficiency of perch-rho(1B) GABA(C) receptors.
- The N-terminal region of perch-rho(1B) contains key residues responsible for pH sensitivity.
Related Concept Videos
01:22Activation and Inactivation of G Proteins
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
01:12GPCR Desensitization
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
01:21G-Protein Gated Ion Channels
GPCRs are primarily responsible for our sense of smell, taste, and vision. The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory organs,...
Sensory organs,...
01:09GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Two...
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
01:23Drugs Acting on Autonomic Ganglia: Stimulants
Ganglionic stimulants activate NM nicotinic receptors in autonomic ganglia, falling into two categories: nicotine mimetics [e.g., lobeline, dimethylpiperazine, tetramethylammonium] and muscarinic receptor agonists [e.g., muscarine, methacholine]. The first category's action is rapid and blocked by nicotinic receptor antagonists, while the second category's action is delayed and blocked by atropine-like agents. Nicotine, an alkaloid, affects the heart rate by stimulating sympathetic or...