Magnesium: NMJ effects

Magnesium plays an essential role in a number of cellular functions, but primarily serves as a physiologic antagonist of calcium. At the NMJ, magnesium interacts via dose-dependent competition with Calcium at presynaptic terminals, leading to inhibition of calcium-dependent acetylcholine release. With less acetylcholine released into the NMJ, there will be a reduction in the depolarization at the motor end-plate, resulting in depressed skeletal muscle fiber membrane excitability. Magnesium works synergistically with nondepolarizing NMBDs, increasing the duration of action and in some cases increasing the speed of onset (see table below). When given in conjunction with depolarizing agents (succinylcholine), magnesium may reduce severity of muscle pains, but does not have a significant effect on the onset or duration of blockade. In patients with Lambert Eaton syndrome or Myasthenia Gravis, magnesium administration can exacerbate weakness as a result of reduction in available acetylcholine. Following tetanic stimulation, we observe tetanic ascent, as opposed to tetanic fade, for magnesium related NM blockade. This is due to successive accumulation of calcium at nerve endings, which increasingly overcomes the competitive antagonism from magnesium.

Magnesium effects at NMJ:

1. Dose-Dependent INHIBITION of Presynaptic Calcium-Dependent ACh release (Major)

2. Direct calcium antagonist effects at muscle fiber (Minor)

3. Prolonged duration of non-depolarizing NMBDs, with minimal change in speed of onset