Biomaterial Database

Conductance and kinetic properties of single nicotinic acetylcholine receptor channels in rat sympathetic neurones. 1991

A Mathie, and S G Cull-Candy, and D Colquhoun

Department of Pharmacology, University College London.

1. The unitary conductance of nicotinic acetylcholine (ACh) receptor channels in rat sympathetic neurones has been studied. Conductance estimates varied from 26-48 pS with a mean of 36.8 pS in 1 mM-Ca2+. The main conductance level varied from patch to patch and the presence (or absence) of additional conductance levels also varied. 2. The channels showed large open channel noise and experiments with 300 mM-NaCl in the patch pipette substantially increased the open channel noise. The appearance of detectable step-like transitions within this noise strongly suggested the existence of closely spaced discrete levels. 3. Removal of divalent cations from the external solution increased the unitary channel conductance. Altering the main permeant ion in divalent-free solutions gave the following conductance sequence: K+ (93 pS) greater than Cs+ (61 pS) greater than Na+ (51 pS) greater than Li+(23 pS). 4. Replacement of Na+ by Cs+ in the external solution considerably reduced the current evoked by ACh in whole-cell recordings and the channel-opening frequency in outside-out patches. 5. The kinetic properties of channels activated by ACh and 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) were also studied. At low concentrations of ACh and DMPP the gap distributions were complex and best fitted by the sum of four exponential components. Individual activations (bursts) were interrupted by the two shortest closed periods the briefer of which had time constants of 36 microseconds for ACh and 67 microseconds for DMPP. 6. The distribution of burst lengths had two components for each agonist, each component making up about 50% of the total area under the distribution. For ACh, the time constant of the longer component (12.2 ms) was similar to the decay time constant of excitatory postsynaptic potentials (EPSCs) at similar temperature and potential. For DMPP the time constant of the longer component was 17.6 ms. 7. The relative number of brief gaps per long burst was much larger for ACh than for DMPP. Therefore the corrected mean open time for ACh (0.86 ms) was much shorter than that for DMPP (2.3 ms). 8. In terms of receptor mechanism, the values of the channel opening equilibrium constant (beta/alpha) estimated from these numbers (ACh, 23; DMPP, 25) suggest that both agonists are efficaceous. 9. DMPP is a potent blocker of the channel with an equilibrium dissociation constant (KB) of around 50 microM and blockage gaps of around 1 ms duration. ACh also blocks the channel but with a higher KB of around 470 microM.(ABSTRACT TRUNCATED AT 400 WORDS)

UI	MeSH Term	Description	Entries
D007473	Ion Channels	Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.	Membrane Channels,Ion Channel,Ionic Channel,Ionic Channels,Membrane Channel,Channel, Ion,Channel, Ionic,Channel, Membrane,Channels, Ion,Channels, Ionic,Channels, Membrane
D008564	Membrane Potentials	The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).	Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D011919	Rats, Inbred Strains	Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.	August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D011978	Receptors, Nicotinic	One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.	Nicotinic Acetylcholine Receptors,Nicotinic Receptors,Nicotinic Acetylcholine Receptor,Nicotinic Receptor,Acetylcholine Receptor, Nicotinic,Acetylcholine Receptors, Nicotinic,Receptor, Nicotinic,Receptor, Nicotinic Acetylcholine,Receptors, Nicotinic Acetylcholine
D004246	Dimethylphenylpiperazinium Iodide	A selective nicotinic cholinergic agonist used as a research tool. DMPP activates nicotinic receptors in autonomic ganglia but has little effect at the neuromuscular junction.	DMPP,1,1-Dimethyl-4-phenylpiperazine Iodide,Dimethylphenylpiperazinium,1,1 Dimethyl 4 phenylpiperazine Iodide,Iodide, 1,1-Dimethyl-4-phenylpiperazine,Iodide, Dimethylphenylpiperazinium
D005260	Female		Females
D005728	Ganglia, Sympathetic	Ganglia of the sympathetic nervous system including the paravertebral and the prevertebral ganglia. Among these are the sympathetic chain ganglia, the superior, middle, and inferior cervical ganglia, and the aorticorenal, celiac, and stellate ganglia.	Celiac Ganglia,Sympathetic Ganglia,Celiac Ganglion,Ganglion, Sympathetic,Ganglia, Celiac,Ganglion, Celiac,Sympathetic Ganglion
D000109	Acetylcholine	A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.	2-(Acetyloxy)-N,N,N-trimethylethanaminium,Acetilcolina Cusi,Acetylcholine Bromide,Acetylcholine Chloride,Acetylcholine Fluoride,Acetylcholine Hydroxide,Acetylcholine Iodide,Acetylcholine L-Tartrate,Acetylcholine Perchlorate,Acetylcholine Picrate,Acetylcholine Picrate (1:1),Acetylcholine Sulfate (1:1),Bromoacetylcholine,Chloroacetylcholine,Miochol,Acetylcholine L Tartrate,Bromide, Acetylcholine,Cusi, Acetilcolina,Fluoride, Acetylcholine,Hydroxide, Acetylcholine,Iodide, Acetylcholine,L-Tartrate, Acetylcholine,Perchlorate, Acetylcholine
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
D012964	Sodium	A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.	Sodium Ion Level,Sodium-23,Ion Level, Sodium,Level, Sodium Ion,Sodium 23