Skeletal muscles AChE activity

Skeletal muscle relaxant activity. Petroleum ether fraction chromatographed and fraction eluted with chloroform, at a concentration of 0.50 mg/mL, was inactive on the frog rectus abdominus muscle vs ACh-induced contractions . 

FIGURE 1.9 Records of the minute electrical currents (downward deflections) that flow through single ligandgated ion channels in the junctional region of frog skeletal muscle. The currents arise from brief transitions of individual nicotinic receptors to an active (channel open) state in response to the presence of various agonists (ACh = acetylcholine SubCh = suberyldicholine DecCh = the dicholine ester of decan-1,10-dicarboxylic acid CCh = carbamylcholine). (From Colquhoun, D. and Sakmann, B., J. Physiol., 369,501-557, 1985. With permission.)... 

The answer is d. (Hardman, pp 142—M3.) ACh will stimulate both muscarinic and nicotinic receptors. Skeletal muscle contraction is mediated through NM receptors, and ganglionic stimulation is an effect of NN receptors All of the other effects listed in the question occur following muscarinic receptor activation and will be blocked by atropine and scopolamine, both of which are muscarinic receptor antagonists. Skeletal muscle contraction will not be affected by these drugs rather, a neuromuscular blocker (e.g., tubocurarine) is required to antagonize this effect of ACh. 

Anticholinesterase agents of all classes can initiate antidromic firing of action potentials in motor neurons, possibly due to an activation of prejunctional ACh receptors that are activated by the elevated synaptic ACh. Quaternary ammonium inhibitors can also act as agonists at these receptors. The initiation of antidromic firing may be a mechanism by which cholinesterase inhibitors produce fasciculation of skeletal muscle. 

L C. Rapacuronium is a skeletal muscle relaxant that works by competing with ACh for receptors at the postjunctional membrane. Nicotine and succinylcholine also act at the end plate receptors but cause depolarization. Hexamethonium is a ganglion blocker that has essentially no activity at the end plate receptors, and scopolamine blocks cholinergic muscarinic receptors and thus does not act at the end plate receptors. 

Pralidoxime Very high affinity for phosphorus atom but does not enter CNS Regenerates active AChE can relieve skeletal muscle end plate block Usual antidote for early-stage (48 h) cholinesterase inhibitor poisoning Intravenous every 4-6 h Toxicity Can cause muscle weakness in overdose... 

Gupta et al. (1987a) demonstrated that selective inhibition of AChE activity in skeletal muscles was apparent within 1 h of soman administration (100 pg/kg, s.c.) in rats when SOL showed the maximum inhibition (87%), whereas EDL showed the least inhibition (47%). AChE activity in skeletal muscles was maximally depressed during the following 3-6 h, the time when animals showed severe signs... 

TABLE 35.1. Normal values of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity in rat skeletal muscles... 

Within 1 h of VX administration (12 ftg/kg, s.c.), AChE activity of all three skeletal muscles was reduced to between 8 and 17% of control with incomplete recovery by the end of 7 days. At the same time, VX caused significant inhibition in the activity of all molecular forms in all three muscles. In EDL, the activity of 4S and lOS showed significant recovery 24 h later, while those of SOL and diaphragm remained inhibited. By day 7, the activity of all forms had recovered and an excess activity was seen in the 4S form of EDL and diaphragm, shifting the latter profile toward that of the EDL and contributing a higher protection to the total AChE activity. 

Compared to AChE activity, butyrylcholinesterase (BuChE, E.C. 3.1.1.8) activity in skeletal muscles is significantly less (Table 35.1). Also, unhke variable AChE activity, all three... 

Smooth muscle is unstriated with innervations from 2 both sympathetic (flight or fight) and parasympathetic (more relaxed) nerves of the autonomic nervous system. E. Smooth muscle appears unstriated under a polarized light microscope, because the myofilaments inside are less or-ganized. Smooth muscle fibers contain actin and myosin myofilaments which are more haphazardly arranged than they are in skeletal muscles. The sympathetic neurotransmitter, Ach, and parasympathetic neurotransmitter, norepinephrine, activate this type of muscle tissue. 

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