Two emerging topics regarding long-range physical signaling in neurosystems: Membrane nanotubes and electromagnetic...

In this review paper, an overview is given of two emerging research topics that address the importance of long-range physical signaling in living biosystems. The first topic concerns the biophysical principles and the physiological significance of long-range cell-to-cell signaling through electrical signals facilitated by membrane nanotubes (MNTs) (also called "tunneling nanotubes"), namely long membrane extensions that connect cells, discovered about 10 years ago. This review paper looks at experimental results that showed electrical signals being propagated through MNTs, and that MNT-mediated electrical coupling between brain cells involves activation of low-voltage-gated calcium channels. The significance of electrical cell-to-cell coupling through MNT for neuronal communication is discussed. The second topic deals with endogenous electromagnetic fields generated by nerve cells. The review concludes that these fields are not just an "epiphenomenon" but play a fundamental role in neuronal processes. For example, electromagnetic fields from brain cells feed back to their generating cells and to other cells (ephaptic coupling) and, for example, modulate the spiking timing of them. It is also discussed that cell membranes of neurons have specific resonance properties which possibly determine the impact of endogenous electric field fluctuations with respect to field strength and frequency. In addition, it is reviewed how traveling and standing waves of the endogenous electromagnetic field produced by neuronal and non-neuronal cells may play an integral part in global neuronal network dynamics. Finally, an outlook is given on which research questions should be addressed in the future regarding these two topics.