Endplate

Del Castillo, J and Katz, B (1957) Interaction at endplate receptors between different choline... 

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... 

Just a year after Stephenson s classical paper of 1956, J. del Castillo and B. Katz published an electrophysiological study of the interactions that occurred when pairs of agonists with related structures were applied simultaneously to the nicotinic receptors at the endplate region of skeletal muscle. Their findings could be best explained in terms of a model for receptor activation that has already been briefly introduced in Section 1.2.3 (see particularly Eq. (1.7)). In this scheme, the occupied receptor can isomerize between an active and an inactive state. This is very different from the classical model of Hill, Clark, and Gaddum in which no clear distinction was made between the occupation and activation of a receptor by an agonist. 

With endplate nicotinic receptors it has been found that, as well as activating the receptor, acetylcholine (ACh) blocks the ion channel. A possible mechanism to describe this situation (assuming for simplicity only a single agonist binding is required to activate the receptor) might therefore be ... 

Hille, B., Ionic Channels of Excitable Membranes, 2nd ed., Sinauer, Sunderland, MD, 1992 (see chap. 7, Endplate channels and kinetics chap. 15, Channel-block mechanisms). 

Edmonds, B., Gibb, A. J., and Colquhoun, D., Mechanisms of activation of muscle nicotinic acetylcholine receptors and the time course of endplate currents, Annu. Rev. Physiol., 57, 469-493, 1995. 

Roberts S et al (1996) Transport properties of the human cartilage endplate in relation to its composition and calcification. Spine (Phila Pa 1976) 21(4) 415 120... 

Boyd LM, Carter AJ (2006) Injectable biomaterials and vertebral endplate treatment for repair and regeneration of the intervertebral disc. Eur Spine J 15(Suppl 3) S414-S421... 

Hamilton DJ et al (2006) Formation of a nucleus pulposus-cartilage endplate construct in vitro. Biomaterials 27(3) 397 105... 

NM receptors—nicotinic-muscular receptors (found in skeletal muscle neuromuscular endplates)... 

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... 

Neurotransmission in autonomic ganglia is more complex than depolarization mediated by a single transmitter 190 Muscarinic receptors are widely distributed at postsynaptic parasympathetic effector sites 190 Stimulation of the motoneuron releases acetylcholine onto the muscle endplate and results in contraction of the muscle fiber 191 Competitive blocking agents cause muscle paralysis by preventing access of acetylcholine to its binding site on the receptor 191... 

The individual subtypes of receptors often show discrete anatomical locations in the peripheral nervous system, and this has facilitated their classification. Nicotinic receptors are found in peripheral ganglia and skeletal muscle. Upon innervation of skeletal muscle, receptors congregate in the junctional or postsynaptic endplate area. Upon denervation or in noninnervated embryonic muscle, the receptors are distributed across the surface of the muscle,... 

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.)... 

Slow-channel syndrome. Abnormally long-lived openings of mutant AChR channels result in prolonged endplate currents and potentials, which in turn elicit one or more repetitive muscle action potentials of lower amplitude that decrement. The morphologic consequences stem from prolonged activation of the AChR channel that causes cationic overload of the postsynaptic region - the endplate myopathy - with Ca2+ accumulation, destruction of the junctional folds, nuclear apoptosis, and vacuolar degeneration of the terminal. Some slow-channel mutations in the transmembrane domain of the AChR render the channel leaky by stabilization of the open state, which is populated even in the absence of ACh. Curiously, some slow-channel mutants can be opened by choline even at the concentrations that are normally present in serum. Quinidine, an open-channel blocker of the AchR, is used for therapy. 

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