Twitch potentiation

AChE at the NMJ is essential in the removal of acetylcholine (ACh) from the synaptic cleft. Inhibition of AChE profoundly modifies neuromuscular transmission, as seen in twitch potentiation, fasciculations. muscular weakness, and acute subjunctional necrosis of muscle fibers. 

Twitch is a muscle contraction caused by a single action potential, whereas tetanus is a sustained muscle contraction caused by a series of repetitive action potentials. The amplitude of tetanus contraction is larger than that of twitch, due to mechanical summation. 

Yamaguchi, T., Caffeine-induced potentiation of twitches in frog single muscle fiber, Japanese Journal of Physiology, 25, 693, 1975. 

A muscle twitch is a brief, weak contraction produced in a muscle fiber in response to a single action potential. While the action potential lasts 1 to 2 msec, the resulting muscle twitch lasts approximately 100 msec. However, a muscle twitch in a single muscle fiber is too brief and too weak to be useful or to perform any meaningful work. In fact, hundreds or thousands of muscle fibers are organized into whole muscles. In this way, the fibers may work... 

As mentioned previously, a single action potential lasting only 2 msec causes a muscle twitch that lasts approximately 100 msec. If the muscle fiber has adequate time to completely relax before it is stimulated by another action potential, the subsequent muscle twitch will be of the same magnitude as the first. However, if the muscle fiber is restimulated before it has completely relaxed, then the tension generated during the second muscle twitch is added to that of the first (see Figure 11.3). In fact, the frequency of nerve impulses to a muscle fiber may be so rapid that there is no time for relaxation in between stimuli. In this case, the muscle fiber attains a state of smooth, sustained maximal contraction referred to as tetanus. 

The amount of tension developed by a muscle fiber during tetanic contraction can be as much as three to four times greater than that of a single muscle twitch. The mechanism involved with this increased strength of contraction involves the concentration of cytosolic calcium. Each time muscle fiber is stimulated by an action potential, Ca++ ions are released from the sarcoplasmic reticulum. However, as soon as the these ions are released, a... 

Figure 11.3 Muscle twitch summation and tetanus. A single action potential (represented by A) generates a muscle twitch. Because duration of the action potential is so short, subsequent action potentials may restimulate the muscle fiber before it has completely relaxed, leading to muscle twitch summation and greater tension development. When the frequency of stimulation becomes so rapid that no relaxation occurs between stimuli, tetanus occurs. Tetanus is a smooth, sustained, maximal contraction.

Initial TOF should demonstrate each successive twitch decreasing in amplitude this is fade. The tetanic stimulus should fail to reach 100% response and should also demonstrate fade. The second TOF should still demonstrate fade but the twitches as a group should have increased amplitude. This is post-tetanic potentiation. 

Succinylcholine is degraded more slowly than is ACh and therefore remains in die synaptic cleft for several minutes, causing an endplate depolarization of corresponding duration. This depolarization initially triggers a propagated action potential (AP) in the surrounding muscle cell membrane, leading to contraction of the muscle fiber. After its i.v. injection, fine muscle twitches (fascicu-lations) can be observed. A new AP can be elicited near the endplate only if the membrane has been allowed to repolarize. 

The earliest signs of CNS toxicity are circumoral and tongue numbness, tinnitus, tremor, and dizziness. These appear at plasma lidocaine (lignocaine) concentrations of about 5 pg-mL-1. The value for prilocaine is similar to lidocaine but bupivacaine toxicity appears at about half those of lidocaine. Further progression is evidenced by drowsiness, visual disturbances, or muscle twitching (plasma lidocaine of 5-10 pg-mL-1). Over 10 p-mL-1 grand mal convulsions, coma and respiratory arrest are likely. Serious CNS toxicity is indicative of imminent and potentially fatal cardiac toxicity since lidocaine is associated with direct cardiac depression at plasma concentrations in excess of 20 pg-mL-1. 

Muscle contraction responses to different patterns of nerve stimulation used in monitoring skeletal muscle relaxation. The alterations produced by a nondepolarizing blocker and depolarizing and desensitizing blockade by succinylcholine are shown. In the train of four (TOF) pattern, four stimuli are applied at 2 Hz. The TOF ratio (TOF-R) is calculated from the strength of the fourth contraction divided by that of the first. In the double burst pattern, three stimuli are applied at 50 Hz, followed by a 700 ms rest period and then repeated. In the posttetanic potentiation pattern, several seconds of 50 Hz stimulation are applied, followed by several seconds of rest and then by single stimuli at a slow rate (eg, 0.5 Hz). The number of detectable posttetanic twitches is the posttetanic count (PTC)., first posttetanic contraction. 

A second antagonist, AM 630 (24b), a novel aminoalkylindole, was found to attenuate the ability of some cannabinoids to inhibit electrically-evoked twitches of the mouse isolated vas deferens [114]. AM 630 was a more potent antagonist of d9-THC than of anandamide (Kd of 14.0 and 278.8 nM, respectively). It was suggested that the receptors for which AM 630 has the highest activity may not be CB, cannabinoid receptors. This is supported by the observation that AM 630 is actually a cannabinoid agonist in the myenteric plexus - muscle preparation [115]. Yamada et al. [116] showed that isothiocyanate derivatives of pravadoline can serve as potential electrophilic affinity ligands for CB],... 

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