Electromagnetic Fields Inhibit Cys-loop Receptor Function by Inducing a Novel Conformational State.

TOLOSA, M.F.; CRAVERO, W.R.; BOUZAT, C.

Baltimore

Congreso; 59th Annual Meeting Biophysical Society; 2015

Biophysical Society

The fact that the general population is increasingly exposed to electromagnetic fields (EMFs) due to the advances in technology raises concern about their potential health effects. There are many gaps in knowledge, particularly at the molecular level, still needing to be filled before better health risk assessments can be made. We therefore studied the influence of EMFs on two Cys-loop receptors: muscle nicotinic (AChR) and 5-HT3A receptors. The transient exposure of cells expressing these receptors to EMFs (15 Hz-120 kHz) significantly decreases the peak current and increases the rise time of macroscopic currents elicited by the agonists. The peak current decreases as a function of EMF frequency (IC50= 54 kHz for AChR). The effects on both receptors are qualitatively similar but more profound for 5-HT3A, indicating different sensitivity to the EMF within the receptor family. To understand the molecular basis leading to the macroscopic changes, we compared single-channel properties before and after the exposure to EMFs. Single-channel amplitude, open duration, duration of activation episodes (clusters) and open probability within clusters are not affected by the EMF. However, EMF leads to a profound decrease of the number of clusters as a direct function of frequency. The analysis reveals that EMFs induce a novel, non conductive, conformational state that arises from the closed resting state through a frequency-dependent transition. Thus, the stabilization of this novel state by EMF sequesters receptors from the activation pathway. Simulations of macroscopic and single-channel currents on the basis of a scheme including this new state well reproduce our experimental data. The identification of a novel conformational state induced by EMF enhances our understanding of receptor function, in general, and of the mechanisms by which EMFs affect neuronal excitability, in particular.