Muscle Type Nicotinic Receptors

Recordings from muscle-type nicotinic receptors contain many brief closures [see Figs, ll.lland 11.13 (below)],with a mean lifetime of around 15 ps at 20 C, and because the shortest event that can be detected reliably is around 20-30 ps, the majority of these are missed (because the durations are exponentially distributed, it is possible to estimate the mean even when observations as short as the mean are missed). Methods have improved since then. Now an exact method for allowing for missed events is available, so it is possible to analyze an entire observed recording by maximum likelihood methods that extract all of the information and that incorporate missed event correction. There are some other methods under development, particularly methods based on the theory of Hidden Markov processes, but none are in routine use. 

Conotoxins that Act on Muscle Receptors. A first grouping is that of toxins that act only on muscle-type nicotinic receptors. 

Methods for recording the currents through single ion channels were developed by Neher and Sakmann (42)and Hamill et al. (43). The theoretical basis for their interpretation was developed initially by Colquhoun and Hawkes (44,45). Far more is known about the muscle-type nicotinic acetylcholine receptor than about any other. The first attempts to investigate the mechanism of action of acetylcholine (ACh) itself were made by Colquhoun and Sakmann (46,47). By that time it was already... 

The calcium permeability of ganglion-type nicotinic receptors is reported to be similar to that of adult muscle in experiments on superior cervical ganglion, intracardiac ganglia, and chromaffin cells, with values for calcium permeability (relative to sodium or cesium) between 0.5 and 1 and fractional current mea-... 

Methonium Compounds. The polymethylene bistrimethyl ammonium series has been investigated since the nineteenth century [see Colquhoun (285)]. This series of compounds consists of two quaternary ammonium groups joined by a polymethylene chain of variable length. They work on both muscle-type and neuronal-type nicotinic receptors, some as agonists and others as antagonists. Their actions were characterized by Paton and... 

Nicotinic receptors (nicotinic acetylcholine receptors, nACHR) exist not only in the membrane of vertebrate skeletal muscle at the synapse between nerve and muscle (muscle-type nAChR) but also at various synapses throughout the brain, mainly at presynaptic positions (neuronal-type nAChR). Whereas the muscle-type nAChR is precisely composed of two a 1-subunits, one (3 -subunit, one y -subunit and one y -subunit (adult)... 

As do most neuronal systems, cholinergic receptors show multiplicity, and we distinguish between nicotinic and muscarinic receptors, which differ in many respects. Whereas acetylcholine (4.1) binds to both types of receptors, the plant alkaloids nicotine (4.2) and muscarine (4.3) trigger a response only from nicotinic or muscarinic cholinergic receptors, respectively. Nicotinic receptors are found in all autonomic ganglia (i.e., in the sympathetic system as well as the parasympathetic) and at the neuromuscular endplate of striated muscle. Muscarinic receptors occur at postganglionic... 

Similar nAChRs are also found in the brain.621 631 632 However, they are not identical but have at least 17 differing amino acid sequences (al-alO, (31-(34, y, 8, and e). The neuromuscular junction receptor (muscle type) from fish is described as (al)2 (31 my / S.626 The brain contains homopentamers of subunits a7, a8, and a9 as well as various heteropentamers. The various forms possess different affinities for acetylcholine and for antagonists such as nicotine.633 634 In the brain the highest affinity for nicotine is shown by an a4 32 form, which represents over 80% of the nAChR in mammalian brain.634 635 Knockout mice in which the (32 subunit gene has been deleted lose their sensitivity to nicotine. 

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