Biomaterial Database

Muscarinic receptors mediate enhancement of spontaneous GABA release in the chick brain. 2000

J Z Guo, and V A Chiappinelli

Department of Pharmacology, The George Washington University, School of Medicine and Health Sciences, Washington, DC 20037, USA.

The functional role of muscarinic acetylcholine receptors in the lateral spiriform nucleus was studied in chick brain slices. Whole-cell patch-clamp recordings of neurons in the lateral spiriform nucleus revealed that carbachol enhanced GABAergic spontaneous inhibitory postsynaptic currents. The duration of the response to carbachol was significantly reduced after blockade of muscarinic receptors with atropine. In the presence of the nicotinic receptor antagonist dihydro-beta-erythroidine, carbachol produced a delayed but prolonged enhancement of spontaneous GABAergic inhibitory postsynaptic currents that was completely blocked by atropine. Muscarine also enhanced the frequency of spontaneous GABAergic inhibitory postsynaptic currents in a dose-dependent manner, but had no effect on inhibitory postsynaptic current amplitude. While 4-diphenylacetoxy-N-(2-chloroethyl)-piperidine hydrochloride, a M3 antagonist, completely blocked muscarine's effect, telenzepine, a M1 antagonist, and tropicamide, a M4 antagonist, only partially decreased the response to muscarine. Pirenzepine, a M1 antagonist, and methoctramine, a M2 antagonist, potentiated muscarine's enhancement of spontaneous GABAergic inhibitory postsynaptic currents. Muscarine's action was blocked by tetrodotoxin, cadmium chloride and omega-conotoxin GVIA, but was not affected by dihydro-beta-erythroidine, 6-cyano-7-nitroquinoxaline-2,3-dione, D(-)-2-amino-5-phosphonopentanoic acid, naloxone or fluphenazine. These results demonstrate that activation of both muscarinic and nicotinic acetylcholine receptors can enhance GABAergic inhibitory postsynaptic currents in the lateral spiriform nucleus. The muscarinic response has a slower onset but lasts longer than the nicotinic effect. The M3 receptor subtype is predominantly involved in enhancing spontaneous GABAergic inhibitory postsynaptic currents. These M3 receptors must be located some distance from GABA release sites, since activation of voltage-dependent sodium channels, and consequent activation of N-type voltage-dependent calcium channels, is required to trigger enhanced GABA release following activation of muscarinic receptors.

UI	MeSH Term	Description	Entries
D009433	Neural Inhibition	The function of opposing or restraining the excitation of neurons or their target excitable cells.	Inhibition, Neural
D011976	Receptors, Muscarinic	One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for MUSCARINE over NICOTINE. There are several subtypes (usually M1, M2, M3....) that are characterized by their cellular actions, pharmacology, and molecular biology.	Muscarinic Acetylcholine Receptors,Muscarinic Receptors,Muscarinic Acetylcholine Receptor,Muscarinic Receptor,Acetylcholine Receptor, Muscarinic,Acetylcholine Receptors, Muscarinic,Receptor, Muscarinic,Receptor, Muscarinic Acetylcholine,Receptors, Muscarinic Acetylcholine
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D002642	Chick Embryo	The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching.	Embryo, Chick,Chick Embryos,Embryos, Chick
D004553	Electric Conductivity	The ability of a substrate to allow the passage of ELECTRONS.	Electrical Conductivity,Conductivity, Electric,Conductivity, Electrical
D005680	gamma-Aminobutyric Acid	The most common inhibitory neurotransmitter in the central nervous system.	4-Aminobutyric Acid,GABA,4-Aminobutanoic Acid,Aminalon,Aminalone,Gammalon,Lithium GABA,gamma-Aminobutyric Acid, Calcium Salt (2:1),gamma-Aminobutyric Acid, Hydrochloride,gamma-Aminobutyric Acid, Monolithium Salt,gamma-Aminobutyric Acid, Monosodium Salt,gamma-Aminobutyric Acid, Zinc Salt (2:1),4 Aminobutanoic Acid,4 Aminobutyric Acid,Acid, Hydrochloride gamma-Aminobutyric,GABA, Lithium,Hydrochloride gamma-Aminobutyric Acid,gamma Aminobutyric Acid,gamma Aminobutyric Acid, Hydrochloride,gamma Aminobutyric Acid, Monolithium Salt,gamma Aminobutyric Acid, Monosodium Salt
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013569	Synapses	Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions.	Synapse
D043587	Receptor, Muscarinic M3	A subclass of muscarinic receptor that mediates cholinergic-induced contraction in a variety of SMOOTH MUSCLES.	Muscarinic Receptor M3,Muscarinic Receptors M3,Receptors, Muscarinic M3,M3 Receptor, Muscarinic,M3 Receptors, Muscarinic,M3, Muscarinic Receptor,M3, Muscarinic Receptors,Muscarinic M3 Receptor,Muscarinic M3 Receptors,Receptor M3, Muscarinic,Receptors M3, Muscarinic
D020864	Calcium Channels, N-Type	CALCIUM CHANNELS that are concentrated in neural tissue. Omega toxins inhibit the actions of these channels by altering their voltage dependence.	N-Type Calcium Channels,Neural-Type Calcium Channels,N-Type Calcium Channel,N-Type VDCC,N-Type Voltage-Dependent Calcium Channels,Calcium Channel, N-Type,Calcium Channels, N Type,Calcium Channels, Neural-Type,Channel, N-Type Calcium,Channels, N-Type Calcium,Channels, Neural-Type Calcium,N Type Calcium Channel,N Type Calcium Channels,N Type VDCC,N Type Voltage Dependent Calcium Channels,Neural Type Calcium Channels,VDCC, N-Type