Digression on chemical electromagnetic field effects in membrane signal transduction - cooperativity paradigm of the acetylcholine receptor

There is ongoing public concern on potential hazards and risks of even small electromagnetic fields (EMFs) such as those emanating from electrical appliances. Evolution and persistence of life in the natural geofields and basic scientific experience in using technical EMFs (F) suggest that, in general, living matter is remarkably stable against external field perturbations within the technical safety limits of the EM field strengths. Besides the trivial primary effects of EMF on ionic charges and dipolar matter, it is explicitly elaborated that cellular biochemical reactivity and channel transport processes are field dependent. However, equilibrium(K) and rate (k) constants are only sensitive to F if the reaction moments DeltaM are finite, as seen in the general van't Hoff relationship d 1n K/dF = DeltaM/RT. Indeed, it is the difference (DeltaM) in the electric or magnetic moments (M), representing the difference in the field forces on the reaction partners. that determines the extent of the field-induced transitions, say from an inactive conformer of a macromolecule to an active one. If small EM fields, which locally can only cause small shifts in K and k, are to become effective for chemical reactivity, amplification is required. A widely encountered concept of chemical amplification is structural, and thus functional, cooperativity, realized in many biopolymers. The cooperation of n units of such a polymer yields a larger DeltaM(n) = n DeltaM and exponentially increases the field sensitivity of the overall equilibrium constant K(n)= K-n. Using the acetylcholine receptor protein as an example for signal amplification by structural cooperativity, explicit proposals are specified for the presumed amplification of small local field effects on proteins of the classical signal transduction cascades. Electric membrane field amplification by interfacial polarization in external fields is discussed in the context of using electric field pulses to transiently permeabilize cells and tissue for the direct transfer of effector substances and genes in cancer and gene therapy. (C) 2000 Elsevier Science B.V. All rights reserved.