Calcium channels neuromuscular junction

In the venom of C. geographus and other fish-hunting species, the conotoxins isolated so far can be divided into three major classes (1-4) o -conotoxms which block neuronal calcium channels at the presynaptic terminus of the neuromuscular junction, a-conotoxins which inhibit the acetylcholine receptor at the postsynaptic terminus, and x-conotoxins which block Na channels on the muscle membrane. 

Calcium channel blockade interferes with prejunctional calcium flux at the neuromuscular junction, and verapamil (but probably not nifedipine) can thus potentiate neuromuscular blockade. Magnesium sulphate, used in management of pre-eclampsia, has a similar effect, and the two drugs in combination may themselves cause neuromuscular block. 

Dodge FA, Jr., Rahamimoff R (1967) Co-operative action a calcium ions in transmitter release at the neuromuscular junction. J Physiol 193 419-32 Dolphin AC (2003) G protein modulation of voltage-gated calcium channels. Pharmacol Rev... 

Fratantoni SA, Weisz G, Pardal AM, Reisin RC, Uchitel OD (2000) Amyotrophic lateral sclerosis IgG-treated neuromuscular junctions develop sensitivity to L-type calcium channel blocker. Muscle Nerve 23 543-550. 

Black Widow spider venom contains several different protein fractions. The most significant component of the venom is the neurotoxin, a-latrotoxin. This neurotoxin acts at the presynaptic membrane of the neuronal and the neuromuscular junctions. The binding of the a-latrotoxin results in the opening of nonspecific cation channels, a massive influx of calcium, release of acetylcholine and norepinephrine and decreased uptake of the neurotransmitter. The neurotransmitter release is most likely responsible for hypertension, muscle fasciculations, and spasms frequently experienced by victims of a bite. Later, generalized muscle weakness and labored breathing may develop in severe cases. While the venom of the black widow spider has been characterized as being more potent than that of many poisonous snakes, the small amount of venom injected limits the degree of toxicity. 

Protti DA, Reisin R, Mackinley TA, Uchitel OD. Calcium channel blockers and transmitter release at the normal human neuromuscular junction. Neurology 1996 46(5) 1391-6. 

Katz E, Ferro PA, Weisz G, Uchitel OD. Calcium channels involved in synaptic transmission at the mature and regenerating mouse neuromuscular junction. J Physiol 1996 497(Pt 3) 687-97. 

Nerves, however, do not always transmit to other nerves. If you touch a hot stove, the end result of all the message transmission has to be that you pull your hand away automatically, and so in this case the final destination of the message is to a different kind of excitable tissue, muscle. The message comes down to the neuromuscular junction, and here the transmitter substance is acetyl choline. In the nerve ending the release of acetyl choline from storage vesicles is triggered by another ion channel event. The depolarisation opens up calcium channels, and the influx of Ca + ions leads to the release of the acetyl choline into the synapse. 

Although most studies of presynaptic toxins are focused on the nerve ending of the neuromuscular junction or synasptosomes, the toxin may have broader biological action. For instance, Mojave toxin inhibits calcium channel dihydropyridine receptor binding in rat brain (Valdes et al., 1989). 

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