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Anion conductance and permeability sequences were obtained for frog skeletal muscle membranes from the changes in characteristic resistance and transmembrane potential after the replacement of one anion by another in the bathing solution. Permeability and conductance sequences are the same. The conductance sequence at pH = 7.4 is C1-> Br-> NO > I-> trichloroacetate > benzoate > valerate >butyrate > proprionate > formate > acetate > lactate > benzenesulfonate > isethionate > methylsulfonate > glutamate > cysteate. The anions are divided into two classes: (a) Chloride-like anions (Cl-through trichloroacetate) have membrane conductances that decrease as pH decreases. The last six members of the complete sequence are also chloride like. (b) Benzoate-like anions (benzoate through acetate) have conductances that increase as pH decreases. At pH = 6.7 zinc ions block C1-and benzoate conductances with inhibitory dissociation constants of 0.12 and 0.16 mM, respectively. Chloride-like and benzoate-like anions probably use the same channels. The minimum size of the channel aperture is estimated as 5.5 X 6.5 A from the dimensions of the largest permeating anions. A simple model of the channel qualitatively explains chloridelike and benzoate-like conductance sequences and their dependence on pH.

The objectives of this investigation were 1) to report that pulmonary surfactant inhibits lipopolysaccharide (LPS)-induced nitric oxide (⋅ NO) production by rat alveolar macrophages, 2) to study possible mechanisms for this effect, and 3) to determine which surfactant component(s) is responsible. ⋅ NO produced by the cells in response to LPS is due to an inducible ⋅ NO synthase (iNOS). Surfactant inhibits LPS-induced ⋅ NO formation in a concentration-dependent manner; ⋅ NO production is inhibited by ∼50 and ∼75% at surfactant levels of 100 and 200 μg phospholipid/ml, respectively. The inhibition is not due to surfactant interference with the interaction of LPS with the cells or to disruption of the formation of iNOS mRNA. Also, surfactant does not seem to reduce ⋅ NO formation by directly affecting iNOS activity or by acting as an antioxidant or radical scavenger. However, in the presence of surfactant, there is an ∼80% reduction in the amount of LPS-induced iNOS protein in the cells. LPS-induced ⋅ NO production is inhibited by Survanta, a surfactant preparation used in replacement therapy, as well as by natural surfactant. ⋅ NO formation is not affected by the major lipid components of surfactant or by two surfactant-associated proteins, surfactant protein (SP) A or SP-C. However, the hydrophobic SP-B inhibits ⋅ NO formation in a concentration-dependent manner; ⋅ NO production is inhibited by ∼50 and ∼90% at SP-B levels of 1–2 and 10 μg/ml, respectively. These results show that lung surfactant inhibits LPS-induced ⋅ NO production by alveolar macrophages, that the effect is due to a reduction in iNOS protein levels, and that the surfactant component responsible for the reduction is SP-B.