Thirty-second Annual Meeting 28 February - 3 March 1988 Phoenix Civic Plaza, Phoenix, Arizona

1988 Biophysical Journal  
31P NMR spectroscopy has been used for over a decade in studies of isolated tissues, anesthetized animals and human subjects. Using this technique the concentrations of energetically important metabolites containing phosphorus can be measured noninvasively and intracellular pH and free Mg2+ can be determined: Changes in these quantities as a result of experimental intervention can be observed. In addition to measuring net reaction rates, in some instances unidirections flux rates for
more » ... reactions can be determined. Applications of this technique to the study of the relation between function and metabolism will be described. Examples and conclusions will be drawn from work in our own and other laboratories, including studies of brain, striated and smooth muscle, red cells and reproductive tissues. W-PM-Sym-2 NMR Investigations of the Control of Mitochondrial Respiration in vivo. Robert S. Balaban. NIH, NHLBI Bethesda MD 20892. NMR has provided new insights into the regulation of cellular metabolism by directly monitoring these processes in vivo. Previous studies relied on extraction residues which suffered from artifacts of the extraction as well as the statistical handicap of paired data. We have been investigating the control of mitochondrial respiration (QO2) in the canine heart in vivo as well as the perfused rat heart and mitochondria in vitro using optical spectroscopy and 31P NMR at 4.7 and 8.5 T. These studies investigated the role of ATP and its hydrolysis products, ADP and Pi, in the feedback control between Q02 and myocardial work by directly measuring [ATP], [CrP], [Pi], free [Mg], NADH, intracellular pH, coronary blood flow and Q02. The free [ADP] was calculated from the creatine kinase (CK) equilibrium and from magnetization transfer measurements of CK exchange rates. These studies demonstrated that over physiological work loads (ie 3 fold changes in Q02) there is little or no change in [ATP] or its hydrolysis products. This suggests that the previous models of respiratory control involving ATP, ADP and Pi alone are either incorrect or must be quantitatively adjusted. An alternative model has been suggested by our data which demonstrate that NADH is an extremely important regulator of Q02. This alternative model suggests that the myocardial Q02 is regulated by the control of substrate oxidation rather than a direct effect of the cytosolic concentrations of ATP or its hydrolysis products. W-PM-Sym-3 1H AND 13C SPECTROSCOPY in vivo. The three-dimensional resolution of proton magnetic resonance imaging is approaching the dimensions of common animal and plant cells, when special receiver coils and gradient coils are used. New possibilities for the study of subtle changes in the biophysical properties of intact, living, optically-opaque objects are suggested by this development. The labelling of cells with magnetic substances, called "contrast agents" in clinical applications, is analogous to the use of stains, fluorescent beads, and the like in optical microscopy. Examples of experiments and calculations will be given. Because the Hodgkin-Huxley approach and derived approaches are phenomenological, a physical theory of excitability is needed. The hypothesis proposed here views excitability as inherent in the dielectric and ion-conducting properties of a transmembrane unit within the channel (HRL, 1987, J. Theor. Biol. 127:321,341). The membrane phenomena of hysteresis, heat block and cold block impose the requirements that the unit be ferroelectric, with upper and lower transition temperatures (Curie points). A mathematical model that differs from classical electrodiffusion only by the addition of two new terms in the dielectric equation of state, ferroelectric electrodiffusion, predicts transverse phase-transition waves accompanied by ion transfer. Using the property of ferroelectrics that a constant biasing field extends the range of polarization, the hypothesis assumes that the majority of ferroelectric channel units in a membrane patch are ferroelectric under the electric field of the resting potential. While a hyperpolarizing field merely increases the polarization, a threshold depolarization lowers the Curie point below the temperature of the unit, which must then undergo a phase transition to a paraelectric state. The transition nusleates at the external surface of the channel unit and carries positive ions A brief review of various theories of excitability of menbranes will be presented. The inhetent assumptions involved, and the limitations of different approaches will be emphasized. The role of physico-chemical constraints, such as mass conservation and tendency towards electroneutrality on the electric potential profile and ion transports, during excitation will be included. 447a 448a While most hydrated phospholipids form non-interdigitated bilayer gel phases, several examples of fully or partially chain-interdigitated lamellar phases have now been observed. Modifications at the polar, interfacial and chain regions of phospholipids can result in complete chain inter- digitation, examples to be discussed from our own studies being S-DPPC, DHPC and lysoPC. On the other hand, alterations in the chain region can lead to partially interdigitated gel phases and examples will be illustrated with our studies of a series of mixed-chain PCs. The structural evidence for the presence of chain-interdigitated phases will be reviewed and the possible mechanism underlying the conversion between non-interdigitated and interdigitated phases will be discussed.
doi:10.1016/s0006-3495(88)83103-5 fatcat:bvqjvcdmhbhz3laazirjnnu6s4