Motor endplate

The inhibition of two cholinesterase activities in blood can also be used to confirm exposure to certain organophosphate ester compounds. Red blood cell acetylcholinesterase is the same cholinesterase found in the gray matter of the central nervous system and motor endplates of sympathetic ganglia. Synonyms for this enzyme include specific cholinesterase, true cholinesterase, and E-type cholinesterase. Plasma cholinesterase is a distinct enzyme found in intestinal mucosa, liver, plasma, and white matter of the central nervous system. Synonyms for this enzyme include nonspecific cholinesterase, pseudocholinesterase, butyrylcholinesterase, and S-type cholinesterase (Evans 1986). Nonspecific cholinesterase is thought to be a very poor indicator of neurotoxic effects. 

According to Fig. 6.17 the nerve cell is linked to other excitable, both nerve and muscle, cells by structures called, in the case of other nerve cells, as partners, synapses, and in the case of striated muscle cells, motor end-plates neuromuscular junctions). The impulse, which is originally electric, is transformed into a chemical stimulus and again into an electrical impulse. The opening and closing of ion-selective channels present in these junctions depend on either electric or chemical actions. The substances that are active in the latter case are called neurotransmitters. A very important member of this family is acetylcholine which is transferred to the cell that receives the signal across the postsynaptic membrane or motor endplate through a... 

Quantal analysis defines the mechanism of release as exocytosis. Stimulation of the motor neuron causes a large depolarization of the motor end plate. In 1952, Fatt and Katz [11] observed that spontaneous potentials of approximately 1 mV occur at the motor endplate. Each individual potential change has a time course similar to the much larger evoked response of the muscle membrane that results from electrical stimulation of the motor nerve. These small spontaneous potentials were therefore called... 

Stimulation of the motoneuron releases acetylcholine onto the muscle endplate and results in contraction of the muscle fiber. Contraction and associated electrical events can be produced by intra-arterial injection of ACh close to the muscle. Since skeletal muscle does not possess inherent myogenic tone, the tone of apparently resting muscle is maintained by spontaneous and intermittent release of ACh. The consequences of spontaneous release at the motor endplate of skeletal muscle are small depolarizations from the quantized release of ACh, termed miniature endplate potentials (MEPPs) [15] (seeCh. 10). Decay times for the MEPPs range between l and 2 ms, a duration similar to the mean channel open time seen with ACh stimulation of individual receptor molecules. Stimulation of the motoneuron results in the release of several hundred quanta of ACh. The summation of MEPPs gives rise to a postsynaptic excitatory potential (PSEP),... 

A neurally derived signaling protein, agrin, acts through a receptor tyrosine kinase, MuSK, in the formation of the specialized postsynaptic endplate by interaction with rapsyn. Thus, MuSK-rapsyn interactions are critical in forming the local scaffold for postsynaptic components in the motor endplate [43,44]. 

FIGURE 43-1 Motor endplates from rabbit intercostal muscle stained with Lowit s gold chloride method, a, terminal axonal arborization b, nucleus d, region where the myelin sheath ends n, neural branch. (From Ramon y Cajal, S. Textura del sistema nervioso del hombre y los vertebrados. Madrid N. Moya, 1899.)... 

An example of a ligand-gated ion channel (B) is the nicotinic cholinocep-tor of the motor endplate. The receptor complex consists of five subunits, each of which contains four transmembrane domains. Simultaneous binding of two acetylcholine (ACh) molecules to the two a-subunits results in opening of the ion channel, with entry of Na+ (and exit of some 1<+), membrane depolarization, and triggering of an action potential (p. 

At low concentration, nicotine is also able to augment the excitability of the motor endplate. This effect can be manifested in heavy smokers in the form of muscle cramps (calf musculature) and soreness. 

Neuromuscular transmission (B) of motor nerve impulses to the striated muscle fiber takes place at the motor endplate. The nerve impulse liberates acetylcholine (ACh) from the axon terminal. ACh binds to nicotinic cholinocep-tors at the motor endplate. Activation of these receptors causes depolarization of the endplate, from which a propagated action potential (AP) is elicited in the surrounding sarcolemma. The AP triggers a release of Ca from its storage organelles, the sarcoplasmic reticulum (SR), within the muscle fiber the rise in Ca concentration induces a contraction of the myofilaments (electromechanical coupling). Meanwhile, ACh is hydrolyzed by acetylcholinesterase (p. 100) excitation of the endplate subsides. if no AP follows, Ca + is taken up again by the SR and the myofilaments relax. 

Muscle relaxants cause a flaccid paralysis of skeletal musculature by binding to motor endplate cholinoceptors, thus blocking neuromuscular transmission (p. 

The transmitter is present throughout the cholinergic neurones and exists within the axon terminals in vesicles. About 1% of the vesicles are the readily releasable store that maintains transmitter release but more than 80% is in motor nerve endings in the releasable store, which is released in response to a nerve impulse. The remainder of ACh is in the so-called stationary store. The release of ACh may be spontaneous or in response to nerve impulses. Spontaneous release of ACh results in the production of random miniature endplate potentials. It is, however, in response to a nerve impulse that we see a large release of ACh provided there is adequate calcium present in the extracellular fluid. Evoked release of ACh usually results in the production of an endplate potential due to depolarisation of the motor endplate. 

ACh receptors are present in the post-junctional membrane of the endplate, in the junctional folds. The nicotinic ACh receptor at the motor endplate has five subunits, two os, (3, 5 and . In addition, a Y subunit instead of an e subunit may be present in the so-called extra-junctional or the fetal receptor. The five subunits are arranged as a cylinder around a central funnel-shaped pore, the ion channel. The two a subunits each carry a recognition site which binds nicotinic agonists such as ACh and antagonists such as the neuromuscular blocking agents. Whilst ACh must bind to both subunits to produce an effect, it is sufficient for... 

Atom description in QSAR models development and use of an atom level index, 22, 1 Autoradiographic investigations of cholinergic and other receptors in the motor endplate, 3, 81 The Binding of drugs to blood plasma macromolecules Recent advances and therapeutic... 

Petrali, J. P., and Mills, K. R. 2001. Microwave-assisted cytochemistry Accelerated visualization of acetylcholinesterase at motor endplates. In Microwave Techniques and Protocols (R.T. Giberson and R.S. Demaree, eds.), pp. 265-172. Humana Press, Totowa NJ. 

Figure 7.2. Stractures of synapses, a Some anatomical variations. Left An intemeural synapse connects two nerve cells. Middle A neuromuscular synapse (also called motor endplate) connects the terminal button of a motoneuron to a skeletal muscle cell. Right An automic nerve cell may form several secretory varicosities that release the transmitter in the target tissue, without forming a circtrmscribed contact zone with an individtral target cell, b Electron microcoscopy of a nemomnsctrlar synapse. The synaptic cleft is very narrow, so that diffusion of secreted transmitter to the receptors on the postsynaptic membrane is fast. Ntrmerous vesicles line up close to the presynaptic membrane. Note the striated myofilament in the postsynaptic cell, c Light microscopy. A single nemon branches out and sends terminal buttorrs to multiple muscle fibers.

As we have seen [in a previous chapter], acetylcholine occurs in s niapses in both the somatic and the autonomic nervous system. The nicotinic acetylcholine receptor is found in the motor endplate of the skeletal muscle, and in both the sympathetic and the parasympathetic ganglia of the peripheral autonomic system. Muscarinic acetylcholine receptors are found at the endings of all secondary neurons within the parasympathetic part of the peripheral autonomous system. In addition, acetylcholine receptors of both types also occur in the brain. Drugs with a useful degree of selectivity for each of these targets are available and used in practical medicine. Selectivity is based on two principles ... 

Succinylcholine has a more sustained action at the motor endplate than acetylcholine has because it is insensitive to the acetylcholinesterase found in the S5uiapse. There is, however, a second variety of cholinesterase that circulates in the blood plasma, also referred to as butyryl-cholinesterase, which cleaves succinylcholine within minutes. This moderately rapid inactivation makes it possible to control the degree of muscle relaxation by adjusting the infusion rate of the agent after discontinuation, the remaining succinylcholine will be swiftly hydrolysed, and the block will subside ... 

Laskowski, M.B., Olson, W.H., Dettham, W-D. (1975). Ultra-structural changes at the motor endplate produced hy an irreversible cholinesterase inhibitor. Exp. Neurol. 47 290-306. 

Melanosomes Motor endplate Nucleus Soluble fraction... 

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