download PDF version - Dr Harold Hillman

transport enzymes, carriers, ion channels, within or near it. All of these macromolecules are largeenough to be seen by the electron microscope, but are not seen at all. The evidence for themcomes from experiments using subcellular fraction, which is a procedure which ignores thesecond law of thermodynamics (Hillman, 1972). Nor has any explanation been offered byelectron microscopists, pharmacologists, cell biologists or biochemists for the invisibility ofthese macromolecules (Hillman, 2008, Ch.20). So I think the conclusion must be that either theyare not present in or near the cell membranes, or that the electron microscope fails to detectthem. I believe the former to be the case.The chemistry of the membranes of the neuron has been assumed to be composed of lipidand protein since the classic experiments of Gorter and Grendel (1925), and the lipid bi-layerhypothesis of Davson and Danielli (1936). This is a very interesting hypothesis originallyworked out for red cell membranes and since assumed to be true for all cell membranes.The orientation of the molecules within the cell membranes is pure speculation; there isno way of proving it, however many elegant diagrams are drawn of it. The finding that one faceappears hydrophobic and the other hydrophilic is not enough evidence upon which to basecurrent models.Meanwhile, one only knows for certain, that the cell membrane appears to consist of onelayer of unknown thickness or chemistry. The diameter of 7-10 nm given in textbooks ismeasured from electron micrographs, and completely ignores any shrinkage of the membranes(of which the two dark lines and one light line are believed to be composed), during thepreparation for electron microscopy.The membranes of cells including neurons are believed to be perforated by tubular ionchannels. These channels are believed to open for particular ions, at particular voltages,particular delays and other parameters. Despite the fact that 30-40 channels have been reportedin the literature (Conley, 1996), only one, the acetylcholine sodium channel, has ever beenclaimed to have been detected by electron microscopy (Unwin and Zampighi, 1980; Toyoshimaand Unwin, 1988). Even the latter represents a construction based on electron microscopy, not adirect image. The same is true of the model by Kistler et al. (1982). Neither Unwin, nor any ofthe other channellers have explained why they so rarely see these allegedly ubiquitous structures.9