At the neuromuscular junction, magnesium acts on the release of acetylcholine and on the excitability of sarcolemma. Verapamil inhibits acetylcholine release and enhances the autodesensitization of acetylcholine receptor ion channels. So, we studied the effect of magnesium on the neuromuscular blocking action of verapamil.

Hemidiaphragm-phrenic nerve preparations were obtained from male Sprague-Dawley rats (200-300 g). Preparations were bathed in Kreb's solution of (mM): NaCl 118, KCl 5, CaCl₂ 2.5, NaHCO₃ 30, KH₂PO₄ 1, MgCl₂ 1 and glucose 11, then maintained at 32℃, and aerated with a mixture of 95% O₂ and 5% CO₂. Isometric forces generated in response to 0.1 Hz and 50 Hz for 1.9 seconds with supramaximal electrical stimulation (0.2 msec, rectangular) to the phrenic nerve, were measured with a force transducer. Single twitch tension (ST) and peak tetanic tension (PTT) were calculated as % reduction versus the control, and tetanic fade (TF) as a % increase. Each preparation was exposed to one of 4 magnesium concentrations of Krebs' solution (0.5, 1.0, 2.0, 3.0 [mM]), and the adequate volume of verapamil stock solution was added to the tissue bath to achieve the desired verapamil concentration. The effects of magnesium and verapamil were allowed to reach a steady state before tension parameters were measured. EC₅, EC₂₅, EC₅₀, EC₇₅, and EC₉₅ of verapamil for ST, PTT and TF were calculated using a probit model. Differences between the EC₅₀'s of verapamil according to magnesium concentrations were tested using the Mann-Whitney U test with the Bonferroni correction, P < 0.05 was regarded as significant.

The effective concentration of verapamil reduced at magnesium concentrations of 0.5, 2.0 and 3.0 (mM).

The neuromuscular action of verapamil was found to be potentiated at either lower or higher magnesium concentrations.