Korean J Anesthesiol.  2004 Jun;46(6):714-718. 10.4097/kjae.2004.46.6.714.

The Effect of Magnesium on the Verapamil Neuromuscular Blockade in Rat Phrenic Nerve-Hemidiaphragm Preparations

• Lee SI
• Lee JH
• Kim DY
• Kim JY

• KMID: 2299080
• DOI: http://doi.org/10.4097/kjae.2004.46.6.714

Abstract

BACKGROUND
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.
METHODS
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 degrees C, 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.
RESULTS
The effective concentration of verapamil reduced at magnesium concentrations of 0.5, 2.0 and 3.0 (mM).
CONCLUSIONS
The neuromuscular action of verapamil was found to be potentiated at either lower or higher magnesium concentrations.

Keyword

magnesium; neuromuscular blockade; rat hemidiaphragm-phrenic nerve; verapamil

MeSH Terms

Acetylcholine
Animals
Baths
Electric Stimulation
Glucose
Humans
Ion Channels
Magnesium Chloride
Magnesium*
Male
Neuromuscular Blockade*
Neuromuscular Junction
Phrenic Nerve
Rats*
Rats, Sprague-Dawley
Refractory Period, Electrophysiological
Sarcolemma
Transducers
Verapamil*
Acetylcholine
Glucose
Ion Channels
Magnesium
Magnesium Chloride
Verapamil