Safety Factor for Neuromuscular Transmission Is Reduced in Mild and Moderate Myasthenia Gravis Due to Loss of Both Sodium Channels and Acetylcholine Receptors (S35.006)

Abstract

Objective: To evaluate the contributions of loss of Na + channels and acteylcholine receptors (AChR) to reduction in safety factor for neuromuscular transmission (SF) in patients with MGFA class IIa and IIIa myasthenia gravis (MG). I hypothesized that loss of endplate Na+ channels would contribute to the reduction of SF in patients with MG. Background Endplate Na + channels improve neuromuscular transmission by reducing the threshold depolarization needed to trigger an action potential (E AP ). In MG, AChRs and Na + channels are lost from the endplate. Na+ channels as well as AChRs were lost from the endplate membrane. Design/Methods: I used standard electrophysiological techniques to compare membrane currents and potentials in intercostal nerve-muscle preparations from 5 MGFA IIIa, 2 MGFA IIa and 7 control adult male subjects. Na + currents recorded using loose patch voltage clamp. Action potential (AP) characteristics measured with a 2 electrode clamp. Endplate potentials (EPPs) studied using μ-conotoxin GIIIb to block muscle Na + channels. The motor nerve was stimulated using a suction electrode. I report the findings for recordings from fast-glycolytic muscle fibers. Results: In MG, EPP was reduced from 40.2 ±1.3 to 30.1±1.3 mV (IIa) and 23.5 ±1.7 mV (IIIa) (p + channel loss increased E AP from −71.9 ±2.2 mV to -66.1 ±2.7 mV (IIa; p AP was the same for MG fibers and controls. The SF for neuromuscular transmission was reduced from 2.98 to 1.58 (IIa) and 1.09 (IIIa). Loss of Na + channels accounted for 53% (IIa) or 41% of the SF reduction. Reduction of EPP produced 47% (IIa) or 59% (IIIa) of the SF decrease. Conclusions: Loss of endplate Na + channels contributes to the reduced SF in MG to a similar extent as does the loss of endplate AChRs. Supported by: Department Veterans Affairs. Disclosure: Dr. Ruff has nothing to disclose.