The cellular microenvironment and signaling through cell membranes.

The structural and functional aspects of communication between cells have been reviewed, with emphasis on the cell membrane in detection and transductive coupling of oscillating electromagnetic fields in the pericellular environment. Imposed fields are powerful and highly specific tools in manipulation of the sequence of events in membrane transductive coupling. They have revealed nonlinear and nonequilibrium aspects of these interactions. In cerebral tissue, extracellular fields orders of magnitude weaker than the membrane potential can modulate cell firing patterns, entrain EEG rhythms, alter neurotransmitter release and modulate behavioral states. These sensitivities have also been widely detected in non-neural tissues. It is therefore proposed that an intrinsic communication system between cells based on these weak electromagnetic influences may be a general biological property. A three-step model of transductive coupling is presented. First, a highly cooperative modification of calcium binding occurs in the plane of the membrane surface following a focal event at a receptor site. This "amplifying" stage releases substantially more energy than in the initial events. Cerebral extracellular conductance changes accompanying physiological responses may arise in perineuronal fluid with a substantial macromolecular content and calcium ions may modulate perineuronal conductivity. In the second stage, coupling occurs along transmembrane helical proteins and may be mediated by solitons. The third stage couples transmembrane signals to the cytoskeleton and to intracellular enzyme systems, including membrane-bound adenylate cyclase and the protein kinase system of intracellular messengers. Activation of these intracellular systems is calcium-dependent.