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Tetanic fade refers to the diminished response from an evoked electrical stimulation of muscle tissue under the effect of either a non-depolarizing neuromuscular blocking agent (ie a "paralytic" agent), or a muscle that is under a phase 2 block of a depolarizing neuromuscular blocking agent.

Overview of the Neuromuscular Signal Transduction
[[File:Synapse diag4.png|thumb|Neuromuscular junction (closer view)

]] In order to transduce an excitatory signal to the muscle, an indication must pass from the presynaptic neuron's axon terminal, travel across the synaptic cleft and be received in the post synaptic muscle tissue's motor end plate to produce the desired effect. The signal that leaves the presynaptic neuron is in the form of Acetylcholine (Ach), a molecule released from stored vesicles at the terminal end of the neuron. Ach travels across the space of the synaptic cleft, and binds to Ach receptors on the sarcolemma of the motor end plate. shortly following its effect, the ach is being degraded by the enzymatic acetylcholinesterase.
 * 1) presynaptic terminal
 * 2) sarcolemma
 * 3) synaptic vesicles
 * 4) Acetylcholine receptors
 * 5) mitochondrion

The Ach receptor is a ligand gated channel that once bound to Ach, goes through a conformational change that allows the flow of calcium, sodium, and potassium down their respective gradient. In adequate numbers, an electrochemical potential will form an endplate potential (EPP), the EPP signal will be propagated through the motor end plate and to the T-tubules to affect the muscle filaments via sodium channels. These sodium channels have a brief activation window, after which they are inactivated until the end plate potential is restored to baseline levels.

For further details on the signal transduction cascade please refer to the Neuromuscular junction page.

Tetanic stimulation and Its Response in normal muscle
Tetany in evoked stimulus, as defined in Morgan & Mikhail's Clinical Anesthesiology as a ~5 seconds of sustained stimulus of between 50 and a 100 Hz. The reaction of muscle tissue to stimulus under no neuromuscular blockade should be equal in intensity throughout the stimulus, The first muscle response and last should be of roughly equal magnitude. Clinically it will present as equal muscle contraction throughout the duration of stimulation.undefined

Tetanic Stimulation in Muscle Tissue Under Non-Depolarizing Neuromuscular Blocking Agent
Non-depolarizing neuromuscular blocking agents (ie Rocuronium, Vecuronium) interact with Ach receptor without activating the channel and prevent the binding of acetylcholine to it. This blocks the signal from the presynaptic neuron, and stops the transduction of the excitatory signal from the synaptic cleft.

Muscle tissue treated with a non-depolarizing neuromuscular blocking agents will demonstrate a diminishing response to tetanic stimulation where the initial intensity will be the the highest, and will produce weaker and weaker response throughout over the course of stimuli. undefined

A some data suggest that this response is due to effect of non-depolarizing neuromuscular blocking agents on the presynaptic nerve, leading to lower acetylcholine secreted to the cleft during the tetanic stimulation. In normal muscle tissue release of Ach works to stimulate more release of Ach from the presynaptic neuron's axon in a positive feedback manner, in tissue under a non-depolarizing neuromuscular blocking agent greatly diminished the levels of Ach that are released into the synaptic cleft. undefined

Tetanic Stimulation in Muscle Tissue Under Depolarizing Neuromuscular Blocking Agent
Depolarizing neuromuscular blocking agents (ie Succinylcholine) employ their effect by binding to the ach receptor and activating it, unlike acetylcholine though, the drug is not rapidly degraded by acetylcholinesterase. Succinylcholine propagates in high concentration for longer duration until it is degraded in the plasma and liver by a different enzyme (pseudocholinesterase). This continues to activate the Ach receptor, and prevents sodium channels from recovering to their active state. This leads to muscle relaxation and termed phase 1 block, clinically it will present as a lower than normal, but equal throughout the stimulation.undefined

Phase 1 block does not show fade under tetanic stimulation. With further administration of depolarizing neuromuscular blocking agent, an effect that is similar to the response of muscle to non-depolarizing neuromuscular blocking agents can be observed. This response, termed phase 2 block, will demonstrate similar fade under tetanic stimulation, a diminishing response to tetanic stimulation where the initial response will be the strongest, and will produce lower and lower response intensity.undefined