Lennon, Vanda A.

ABSTRACTIntroductionAll descriptions of the Lambert–Eaton syndrome are based on symptomatic patients. We incidentally encountered electromyographic evidence of this syndrome in a patient being studied for another reason. The patient had controlled hypothyroidism and smoked for 9 pack‐years but never had symptoms of weakness or had evidence of cancer. Methods: Detailed electrophysiological and serological evaluations were undertaken in this study. Results: Neuromuscular transmission tests were consistent with a presynaptic disorder. Autoantibodies specific for P/Q‐type voltage‐gated calcium channels (VGCC) were detected in the serum and persisted throughout 7 years of follow‐up. Multiple IgG markers of thyrogastric autoimmunity also were detected. Conclusions: This demonstration of asymptomatic Lambert–Eaton syndrome persisting for 8 years provided novel insight into the natural history of the disorder. It is plausible that patients with a subclinical syndrome would have abrupt neuromuscular decompensation when challenged with medications that compromise the safety factor for synaptic transmission. Muscle Nerve 49: 764–767, 2014

We previously reported that activation of muscarinic acetylcholine receptors (mAChR) of M3 subtype causes hydrolysis of phosphoinositides and inhibits voltage-gated Ca2+ channel activity in small cell lung carcinoma (SCLC) cells. We now report that mAChR activation causes exponentially growing SCLC cells to arrest in S and G2/M phases of the cell cycle, concomitant with a decrease in DNA synthesis. Cell cycle progression and DNA synthesis resume when mAChR are down-regulated. In serum-starved SCLC cells, mAChR activation inhibits DNA synthesis induced by serum, bombesin, insulin, or insulin-like growth factor-I. The finding that DNA synthesis is inhibited even when mAChR are activated after exposure of cells to growth factors indicates that decreased signal transduction by growth factor receptors is not the mechanism of mAChR-mediated growth inhibition. Our data suggest that mAChR activation disrupts a common event that is induced by different growth factors and is fundamental for cell cycle progression.