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Local anesthetics (LA) have been found to interact with phospholipids and lipids extracted from nerve and muscle. This reaction is demonstrated by: (a) Inhibition by LA of phospholipid (and tissue lipid) facilitated transport of calcium from a methanol: water phase into chloroform. This action is dependent upon the cationic form of the LA. (b) LA increase the electrical resistance of "membranes" prepared by impregnating Millipore filters with cephalin:cholesterol or tissue lipid extracts and bathed with NaCl or KCl solutions. (c) LA coagulate aqueous dispersions of cephalin, phosphatidyl serine, phosphatidyl ethanolamine, and inositide, an action shared by calcium. The order of potency in coagulating cephalin sols is tetracaine > calcium > butacaine > procaine. Na(+) and K(+) do not coagulate phospholipid dispersions at 0.1 M concentration and antagonize the effect of Ca(2+). (d) LA produce a marked fall in the pH of cephalin sols equivalent to that produced by calcium, (e) Ca(2+) and LA form 1:2 molar complexes with phospholipids probably by ion-ion and ion-induced polar type of binding at the phosphate groups of the lipid. It is suggested that such reactions with cell membrane phospholipids may underlie inhibitory effects of LA on cellular ion fluxes and provide a chemical basis for anesthetic action.

The effects of various neutral salts on the temperature of the thermally-induced denaturation of the globular protein ribonuclease are described and compared with the effects of these salts on helix-coil transition temperatures in other macromolecules. These agents affect the stability of the native form of macromolecules as diverse as ribonuclease, collagen, DNA, and myosin in very similar ways; salts such as KSCN and CaCl(2) serve as very potent general structural destabilizers or denaturants, while salts such as (NH(4))(2)SO(4) and K(2)HPO(4) strongly stabilize the native conformation. The effectiveness of the neutral salts as ribonuclease destabilizers is compared with that of urea and the guanidinium salts.

The variations in the membrane potentials of skeletal muscle fibers which follow high rates of sodium extrusion are not due to changes in the ionic concentrations of the fiber; experiments suggest that sodium is extruded by an electrogenic mechanism.