Biomaterial Database

End-plate currents and acetylcholine noise at normal and myasthenic human end-plates. 1979

S G Cull-Candy, and R Miledi, and A Trautmann

1. The amplitudes and time courses of miniature end-plate currents (m.e.p.c.s) have been compared at normal and myasthenic (MG) human end-plates studied under voltage clamp. The m.e.p.c. amplitude at MG end-plates is reduced to about one third normal; mean m.e.p.c. (normal) = 2.6 +/- 0.2 nA, mean m.e.p.c. (MG) = 1.0 +/- 0.1 nA. The decay time constant of m.e.p.c.s (tau m.e.p.c.) is very similar at normal and MG end-plates; tau m.e.p.c. (normal) = 1.70 +/- 0.1 msec, tau m.e.p.c. (MG) = 1.80 +/- 0.13 msec (Vm = - 80 mV. T = 23 degrees C). 2. The equilibrium potential of the end-plate current (e.p.c.) at normal and myasthenic human end-plates is close to 0 mV. 3. Decay time constants tau e.p.c. and tau m.e.p.c. increase exponentially with membrane hyperpolarization. The voltage sensitivity of the time constants was similar at normal and MG end-plates. 4. Both normal and myasthenic e.p.c.s are greatly prolonged in the presence of neostigmine (10(-6) g/ml.). At the same time the voltage sensitivity of tau e.p.c. is slightly reduced. 5. In response to steady ionophoretically applied ACh the mean membrane currents obtained at MG end-plates were smaller than the normal under similar conditions. 6. Analysis of end-plate current noise obtained during the steady application of acetylcholine (ACh) to voltage clamped normal and MG human end-plates showed that the amplitude of the elementary current event (gamma) and the average channel life-fime (tau noise) was similar at the two sites: tau noise (normal) - 1.54 +/- 0.04 msec, tau noise (MG) = 1.60 +/- 0.11 msec; gamma(normal) - 22.3 +/- 1.57 PS, gamma (MG) = 20.25 +/- 1.93 pS (Vm = - 80 mV, T = 23 degrees C). The voltage sensitivity of the channel life time, measured from end-plate current noise, was similar at normal and MG end-plates. 7. At normal human end-plates a packet of transmitter opens about 1500 channels whereas at MG end-plates a packet opens only about 600 channels. It is calculated that the size of the transmitter packets released from MG-terminals is at least as large as the packet of the ACh released from normal human nerve terminals.

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
D009045	Motor Endplate	The specialized postsynaptic region of a muscle cell. The motor endplate is immediately across the synaptic cleft from the presynaptic axon terminal. Among its anatomical specializations are junctional folds which harbor a high density of cholinergic receptors.	Motor End-Plate,End-Plate, Motor,End-Plates, Motor,Endplate, Motor,Endplates, Motor,Motor End Plate,Motor End-Plates,Motor Endplates
D009132	Muscles	Contractile tissue that produces movement in animals.	Muscle Tissue,Muscle,Muscle Tissues,Tissue, Muscle,Tissues, Muscle
D009157	Myasthenia Gravis	A disorder of neuromuscular transmission characterized by fatigable weakness of cranial and skeletal muscles with elevated titers of ACETYLCHOLINE RECEPTORS or muscle-specific receptor tyrosine kinase (MuSK) autoantibodies. Clinical manifestations may include ocular muscle weakness (fluctuating, asymmetric, external ophthalmoplegia; diplopia; ptosis; and weakness of eye closure) and extraocular fatigable weakness of facial, bulbar, respiratory, and proximal limb muscles. The disease may remain limited to the ocular muscles (ocular myasthenia). THYMOMA is commonly associated with this condition.	Anti-MuSK Myasthenia Gravis,MuSK MG,MuSK Myasthenia Gravis,Muscle-Specific Receptor Tyrosine Kinase Myasthenia Gravis,Muscle-Specific Tyrosine Kinase Antibody Positive Myasthenia Gravis,Myasthenia Gravis, Generalized,Myasthenia Gravis, Ocular,Anti MuSK Myasthenia Gravis,Generalized Myasthenia Gravis,Muscle Specific Receptor Tyrosine Kinase Myasthenia Gravis,Muscle Specific Tyrosine Kinase Antibody Positive Myasthenia Gravis,Myasthenia Gravis, Anti-MuSK,Myasthenia Gravis, MuSK,Ocular Myasthenia Gravis
D009388	Neostigmine	A cholinesterase inhibitor used in the treatment of myasthenia gravis and to reverse the effects of muscle relaxants such as gallamine and tubocurarine. Neostigmine, unlike PHYSOSTIGMINE, does not cross the blood-brain barrier.	Synstigmin,Neostigmine Bromide,Neostigmine Methylsulfate,Polstigmine,Proserine,Prostigmin,Prostigmine,Prozerin,Syntostigmine,Bromide, Neostigmine,Methylsulfate, Neostigmine
D009469	Neuromuscular Junction	The synapse between a neuron and a muscle.	Myoneural Junction,Nerve-Muscle Preparation,Junction, Myoneural,Junction, Neuromuscular,Junctions, Myoneural,Junctions, Neuromuscular,Myoneural Junctions,Nerve Muscle Preparation,Nerve-Muscle Preparations,Neuromuscular Junctions,Preparation, Nerve-Muscle,Preparations, Nerve-Muscle
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
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
D013997	Time Factors	Elements of limited time intervals, contributing to particular results or situations.	Time Series,Factor, Time,Time Factor