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 smal l electromagnetic fields (EMFs) such as those emanating from electrical app liances. Evolution and persistence of life in the natural geofields and bas ic scientific experience in using technical EMFs (F) suggest that, in gener al, 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 e xplicitly elaborated that cellular biochemical reactivity and channel trans port processes are field dependent. However, equilibrium(K) and rate (k) co nstants 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. Indee d, it is the difference (DeltaM) in the electric or magnetic moments (M), r epresenting the difference in the field forces on the reaction partners. th at determines the extent of the field-induced transitions, say from an inac tive conformer of a macromolecule to an active one. If small EM fields, whi ch locally can only cause small shifts in K and k, are to become effective for chemical reactivity, amplification is required. A widely encountered co ncept of chemical amplification is structural, and thus functional, coopera tivity, realized in many biopolymers. The cooperation of n units of such a polymer yields a larger DeltaM(n) = n DeltaM and exponentially increases th e field sensitivity of the overall equilibrium constant K(n)= K-n. Using th e 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 si gnal transduction cascades. Electric membrane field amplification by interf acial 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.