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I I ti .`. Ae. . 1 . , . ~., .~.. ~..~ ~ ~ Ttta: CouxciL FOR Tosacca RssLARCa-U.$.A., INC. , Memorandum To: Dr. S.C. Somm ers From: D.H. Ford SF Re: Site visit with Dr. A. McLaughlin, Brookhaven National Laboratory, Upton, N.Y. October 13th, 1982 Grant No. 149 3; Title: 'Interaction of Divalent Cations with Model and Biological Membranes.' Overview: As stated in Dr. McLaughlin's proposal, his object: are to examine the molecular mechanisms by which divalent cations such as calcium (Ca) interact with bilayer membranes formed from phospholipids and glycolipids (model membranes). Thus, he will be determining the divalent cation binding sites and their abilil to induce lateral phase separation in membranes formed from mix- tures of neutral and charged lipids. This should eventually en- hance our understanding of the significance of the interaction of such cations with the bilayer component of cellular and sub- cellular membranes. A second related objective concerns his in- terest in examinin g the interaction of Ca with the chromaffin granule membranes so as to induce release of the granule compo- nents (ATP and epinephrine). He believes that Ca binds to the surface of the chromaffin granule membrane to induce a K flux which is coupled t o the flux of a proton to cause an increase in osmotic pressure and the subsequent disruption of the membrane causing exocytosis of the contents of the granule (ATP and epinephrine). Biological significance: Important in understanding release of secretory products into blood or extracellular spaces; important in understanding role of Ca and other ions in determinir surface potential of such membranes Is neurons and muscles in relation to Na~K and Cl channels and conductance. A basic question i n such studies is: " When divalent cations change the electrical potential of a membrane receptor site, do the cations bind to the charge on a membrane ot near it or to a specific receptor or do they merely screen the charge or receptor on the membrane? Techonolgy of NMR: Dr. McLaughlin'provided an elegant lucid review of Nuclear Magnetic Resonance, which i.s a spectroscopic technique based on a static magnetic field and a radio frequency field causing a rotational effect on the nucleus of an-•atom of 'carbon, phosphorus or hydrogen to provide a measurable perturba- tion of the field as a function of that particular radio frequenc This can provide information about the physical characteristics of a molecule (more precisely, specific atoms - C, P,'H- within a molecule).