Effect of neutral salts on the interaction of rat brain hexokinase with the outer mitochondrial membrane.

The glucose 6-phosphate (Glc-6-P)-induced solubilization of mitochondrial hexokinase (ATP:d-hexose 6-phosphotransferase, EC 2.7.1.1) from rat brain can be reversed by low concentrations (ionic strength <~0.02 m) of neutral salts. When compared to the original particulate enzyme (i.e., enzyme found on the particles prior to solubilization by Glc-6-P), the rebound enzyme is similar in distribution on sucrose gradients, K_m for ATP, inhibition by antiserum to purified brain hexokinase, and resistance to removal by exhaustive washing of the particles. The effectiveness of chloride salts at promoting rebinding increases in the order Cs⁺< Rb⁺< K⁺≤ Na⁺< Li⁺< Mg²⁺. This salt-induced rebinding is attributed to the screening of negative charges on the enzyme and/or membrane by cations, thereby decreasing repulsive forces and enhancing attractive interactions between enzyme and membrane. Solubilization of the enzyme, both in the presence and absence of Glc-6-P, is increased at alkaline pH, as would be expected due to increasing repulsive interactions between negative charges on membrane and enzyme as the pH is increased beyond the pI of the enzyme (pI = 6.3). In contrast to previous interpretations, P_i displayed no special efficacy at reversing Glc-6-P-induced solubilization, being comparable to other neutral salts on an ionic strength basis. However, P_i and its structural analog, arsenate, were shown to counteract specifically the Glc-6-P-induced inhibition and conformational change in the enzyme. At higher concentrations (ionic strength >~ 0.02 m) neutral salts themselves lead to reversible dissociation of the enzyme from the mitochondria. The efficacy of the salts depends primarily on the pH and on the position of the anion in the Hofmeister series, with salts of chaotropic anions (SCN^?, I^?, Br^?) being most effective. At pH 6, both chaotropic and nonchaotropic salts solubilize the enzyme, while at pH 8.5, only the chaotropes retain this ability. Neutral salts also have a reversible effect on the conformation of the enzyme, as reflected by enzymatic activity, with chaotropic salts again being most effective; there is no pronounced influence of pH (in the range of pH 6–8.5) on the ability of the salts to cause conformational change in the enzyme. Based on a lack of correlation between saltinduced solubilization and conformational changes affecting activity, it is concluded that the latter are not directly responsible for release of the enzyme from the membrane. In the presence of KSCN, the extent of solubilization decreased with increase in temperature, indicating a negative enthalpy for solubilization. In contrast, in the absence of salt, the enthalpy for solubilization was positive. These temperature effects and the effects of neutral salts on the hexokinase-membrane interaction are interpreted in terms of a model in which electrostatic forces are considered to be of major importance. At low ionic strength, repulsive forces between negative charges on enzyme and membrane predominate; screening of these charges by cations diminishes the repulsion, effectively enhancing attractive electrostatic forces between enzyme and membrane and thus promoting their interaction. At higher ionic strengths, the attractive electrostatic forces are themselves disrupted, resulting in dissociation of the enzyme from the membrane. It is proposed that the greater effectiveness of chaotropic salts at disrupting these attractive forces is due to their increased ability to penetrate through hydrophobic regions of enzyme and membrane to relatively inaccessible sites of electrostatic-interaction.     

A comparative study on the hydrodynamic shape, conformation, and stability of E. coli ribosomal subunits in reconstitution buffer.

We have compared the hydrodynamic shape, conformation, and stabilities of active, unwashed ribosomal subunits, as well as their susceptibilities to changes in temperature and ionic strength. Both intrinsic viscosity and sedimentation velocity measurements indicate that the 30 S subunit has a more asymmetric hydrodynamic shape. The intrinsic viscosity of this subunit in reconstitution buffer has been found to be significantly larger than the value reported previously. While the RNA conformation in both subunits may be very similar as suggested by the near uv CD spectra, the average conformation of the protein in the two subunits is drastically different. The 30 S subunit has a lower T_m. The 50 S subunit is rather stable toward changes of ionic strength, whereas the 30 S subunit is quite susceptible to changes in ionic strength.     

Intracellular magnesium crystallized in the arteries and myocardium: New chemical-physical hypothesis

Detailed monitoring of Mg in the body should reveal five interacting chemical pools: pool 1 with the free, ionic, and most mobile Mg in chemical equilibrium with the others; pool 2 with the Mg salts precipitated mainly in the arteries and myocardium; pool 3 and 4, two different reservoirs of Mg; pool 5 with the physiologically bound Mg. The pool size needs to be determined exactly. The Mg content of the mitochondria in the arteries and myocardium is less than the content of K and greater than the content of Ca. These elements are in close equilibrium with each other and with PO^3?₄. Only within certain limits can the body adjust itself to the interdependent changes of these ions; it is, therefore, important that their combined presence, rather than Mg alone, be quantitatively determined.When the solubility products of Mg₃(PO₄)₂.8H₂O or of MgKPO₄ are reached, the two salts precipitate inside the cells, seeding further irreversible crystallization of CaMgK. TriMg phosphate nucleates triCa phosphate and the two cause the sarcoma to be filled with tightly packed crystals. On the inside surface of the membrane electromagnetic interactions exist with the polar salts in solution, which form a kind of fluid layer adherent to the membrane. Crystallization of MgKPO₄ occurs solely at this interface, where the K_sp is reached. The salt becomes polarly coupled with the membranes and, together, they favor successive epitaxial crystallization. After several decades the entire arterial wall is “calcified” and arteriosclerosis is in a well advanced stage; myocardial scars and other cardiovascular lesions should originate in a similar way.     

Loss of function of biomembranes and solubilization of membrane proteins during freezing

Isolated thylakoid membranes are damaged during freezing in dilute salt solutions, as shown by the inactivation of photochemical thylakoid reactions. After freezing, a number of membrane proteins were found in the particle-free supernatant. Up to 5% of the total membrane protein was solubilized by freezing, and the pattern of released proteins as seen in sodium dodecyl sulfate gel electrophoretograms was influenced by the nature of the solutes present. Membranes protected by sucrose did not release much protein during freezing. Concentrated salt solutions caused protein release also in the absence of freezing. Among the proteins released were ferredoxin—NADP⁺ reductase, plastocyanin and coupling factor CF₁. Subunits of CF₁ were found in different proportions in the supernatants of thylakoid suspensions after freezing in the presence of different salts. Cyclic photophosphorylation was largely inactivated before significant protein release could be detected.It is suggested that protein release is the final consequence of the non-specific suppression of intramembrane ionic interactions by the high ionic strength created in the vicinity of the membranes by the accumulation of salts during slow freezing. Salt effects on water structure and alterations of nonpolar membrane interactions by the incorporation of (protonated) lipophilic anions from organic salts into the membrane phase during freezing may also be involved.     

PHOTOADAPTATION AND THE “PACKAGE” EFFECT IN DUNALIELLA TERTIOLECTA (CHLOROPHYCEAE)1

In the marine unicellular chlorophyte, Dunaliella tertiolecta Butcher, the spectrally averaged m vivo absorption cross section, normalized to chlorophyll a (so-called a* values), vary two-fold in response to changes in growth irradiance. We used a kinetic approach to examine the specific factors which account for these changes in optical properties as cells photoadapt. Using Triton X-100 to solubilize membranes, we were able to differentiate between “package” effects and pigmentation effects. Our analyses suggest that 43–49% of the variability in a* is due to changes in pigmentation, whereas 51–57% is due to the “package” effect. Further analyses revealed that changes in cell sue did not significantly affect packaging, while thylakoid stacking and the transparency of thylakoid membranes were important factors. Our results suggest that thylakoid membrane protein/lipid ratios change during photoadaptation, and these changes influence the effective rate of light harvesting per unit chlorophyll a.     

Preparation of membrane vesicles from isolated myelin. Studies on functional and structural properties

Myelin membranes purified from bovine brain are shown to form membrane vesicles when incubated in hypotonic buffer. Following restoration of isotonicity a resealing of the membrane occurs as judged by a significant decrease in ²²Na⁺ permeability. Electron spin resonance measurements using stearic acid spin label I indicate a small decrease in membrane fluidity with increasing ionic strength between 50 and 80 mM NaCl. Iodination of myelin membrane vesicles by lactoperoxidase shows a four-fold increase in the amount of iodine incorporation into the myelin basic protein from 0–150 mM NaCl, while the iodination of the proteolipid protein remains essentially unaffected by the change in ionic strength. This dependence of the iodination of the myelin basic protein on the ionic strength can be explained by the electrostatic interactions of this protein with membrane lipids. In view of striking analogies with studies on model membranes correlating protein binding with membrane permeability changes, we suggest a similar structure-function relationship for the myelin basic protein.     

Millimeter microwave effect on ion transport across lipid bilayer membranes

The effects of millimeter microwaves in the frequency range of 54–76 GHz on capacitance and conductance of lipid bilayer membranes (BLM) were studied. Some of the membranes were modified by gramicidin A and amphotericin B or by tetraphenylboron anions (TPhB_?). The millimeter microwaves were pulse-modulated (PW) at repetition rates ranging from 1 to 100 pps, PW at 1000 pps, or unmodulated continuous waves (CW). The maximum output power at the waveguide outlet was 20 mW. It was found that CW irradiation decreased the unmodified BLM capacitance by 1.2% ± 0.5%. At the same time, membrane current induced by TPhB transport increased by 5% ± 1%. The changes in conductance of ionic channels formed by gramicidin A and amphotericin B were small (0.6% ± 0.4%). No “resonance-like” effects of mm-wave irradiation on membrane capacitance, ionic channel currents, or TPhB transport were detected. All changes in membrane capacitance and currents were independent of the modulation employed and were equivalent to heating by approximately 1.1 °C. © 1995 Wiley-Liss, Inc.     

Intrinsic electric fields and proton diffusion in immobilized protein membranes. Effects of electrolytes and buffers.

We present a theory for proton diffusion through an immobilized protein membrane perfused with an electrolyte and a buffer. Using a Nernst-Planck equation for each species and assuming local charge neutrality, we obtain two coupled nonlinear diffusion equations with new diffusion coefficients dependent on the concentration of all species, the diffusion constants or mobilities of the buffers and salts, the pH-derivative of the titration curves of the mobile buffer and the immobilized protein, and the derivative with respect to ionic strength of the protein titration curve. Transient time scales are locally pH-dependent because of protonation-deprotonation reactions with the fixed protein and are ionic strength-dependent because salts provide charge carriers to shield internal electric fields. Intrinsic electric fields arise proportional to the gradient of an "effective" charge concentration. The field may reverse locally if buffer concentrations are large (greater to or equal to 0.1 M) and if the diffusivity of the electrolyte species is sufficiently small. The "ideal" electrolyte case (where each species has the same diffusivity) reduces to a simple form. We apply these theoretical considerations to membranes composed of papain and bovine serum albumin (BSA) and show that intrinsic electric fields greatly enhance the mobility of protons when the ionic strength of the salts is smaller than 0.1 M. These results are consistent with experiments where pH changes are observed to depend strongly on buffer, salt, and proton concentrations in baths adjacent to the membranes.     

The Changes of “Myosin B” during Storage of Rabbit Muscle

The process of the denaturation of “myosin B” solution was studied by the measurement of ATPase activity, SH groups, sedimentation behaviour and flow birefringence. When “myosin B” solution was stored at lower temperature, lower pH or higher ionic strength, the interaction between myosin A and actin became less strong, and further storage brought about an irreversible dissociation.

The condition for measuring Mg-modified ATPase activity of “myosin B” at low ionic strength was explained in the relation with superprecipitation.     

A Neutron Scattering Study of the Ternary Complex EF-Tu•GTP-valy1-tRNAVal 1A

Abstract

The complex formation between elongation factor Tu (EF-Tu), GTP, and valyl-tRNA^Val _1A has been investigated in a hepes buffer of “pH” 7.4 and 0.2 M ionic strength using the small-angle neutron scattering method at concentrations of D₂O where EF-Tu (42% D₂O) and tRNA (71% D₂O) are successively matched by the solvents. The results indicate that EF-Tu undergoes a conformational change and contracts as a result of the complex formation, since the radius of gyration decreases by 15% from 2.82 to 2.39 nm. tRNA^Val _1A, on the other hand, seems to mainly retain its conformation within the complex, since the radii of gyration for the free (after correction for interparticular scattering) and complexed form are essentially the same. 2.38 and 2.47 nm, respectively.     

Flexible Composite Solid Electrolyte Facilitating Highly Stable “Soft Contacting” Li–Electrolyte Interface for Solid State Lithium‐Ion Batteries

A flexible composite solid electrolyte membrane consisting of inorganic solid particles (Li_1.3Al_0.3Ti_1.7(PO₄)₃), polyethylene oxide (PEO), and boronized polyethylene glycol (BPEG) is prepared and investigated. This membrane exhibits good stability against lithium dendrite, which can be attributed to its well‐designed combination components: the compact inorganic lithium ion conducting layer provides the membrane with good mechanical strength and physically barricades the free growth of lithium dendrite; while the addition of planar BPEG oligomers not only disorganizes the crystallinity of the PEO domain, leading to good ionic conductivity, but also facilitates a “soft contact” between interfaces, which not only chemically enables homogeneous lithium plating/stripping on the lithium metal anode, but also reduces the polarization effects. In addition, by employing this membrane to a LiFePO₄/Li cell and testing its galvanostatic cycling performances at 60 °C, capacities of 158.2 and 94.2 mA h g^?1 are delivered at 0.1 C and 2 C, respectively.     

Effects of phase transitions on enzymes bound to different cellular membranes

Summary In unfixed cryostat sections enzymes attached to various cellular membranes differ in their sensitivity to the inhibitory effects of Ca and CNS ions. Similar differences between enzymes related to various membranes were also noted in the possibility of reversing the inhibition of NaCl treatment and in the effects of oxygen in rendering the inhibition irreversible.Evidence was adduced to show that some of the previous data on reversibility of ionic inhibition of membrane bound enzymes were due to an inadvertently introduced step of drying. The effect of drying was not apparent in NaCl-treated sections. In CaCl²- and KCNS-treated sections the effect of drying was due to a high concentration of the salts prevailing during evaporation and to atmospheric oxygen. A possible effect of denaturation not associated with oxidation could not be excluded.A summary of this report has been presented at the International Congress of Histochemistry and Cytochemistry in New York in August 1968.     

Ion-induced alterations of the local hydration environment elucidate Hofmeister effect in a simple classical model of Trp-cage miniprotein

Protein stability is known to be influenced by the presence of Hofmeister active ions in the solution. In addition to direct ion-protein interactions, this influence manifests through the local alterations of the interfacial water structure induced by the anions and cations present in this region. In our earlier works it was pointed out that the effects of Hofmeister active salts on the stability of Trp-cage miniprotein can be modeled qualitatively using non-polarizable force fields. These simulations reproduced the structure-stabilization and structure-destabilization effects of selected kosmotropic and chaotropic salts, respectively. In the present study we use the same model system to elucidate atomic processes behind the chaotropic destabilization and kosmotropic stabilization of the miniprotein. We focus on changes of the local hydration environment of the miniprotein upon addition of NaClO₄ and NaF salts to the solution. The process is separated into two parts. In the first, ‘promotion’ phase, the protein structure is fixed, and the local hydration properties induced by the simultaneous presence of protein and ions are investigated, with a special focus on the interaction of Hofmeister active anions with the charged and polar sites. In the second, ‘rearrangement’ phase we follow changes of the hydration of ions and the protein, accompanying the conformational relaxation of the protein. We identify significant factors of an enthalpic and entropic nature behind the ion-induced free energy changes of the protein-water system, and also propose a possible atomic mechanism consistent with the Collins’s rule, for the chaotropic destabilization and kosmotropic stabilization of protein conformation.     

Electrical-ionic control of gene expression

• 1.1. Changes in turgor, in cell volume, in membrane potential, in intracellular ionic activities and, more recently, in spontaneous electrical activity have been reported to be causally linked to the expression of specific genes.
• 2.2. As a result, it has become clear that changes in membrane properties and/or in the intracellular “ionic environment” can play an important role in generating cell type specific physiological responses which indirectly—or maybe directly—affect gene expression.
• 3.3. Possible targets of the ionic “environment” are: the selective transport across biological membranes; the activity of certain (regulatory) enzymes; the conformation of some (regulatory) proteins; of chromatin; of the cytoskeleton; of the nuclear matrix; the association of the cytoskeleton with plasmamembrane proteins or RNA; the association chromatin-nuclear matrix; protein-DNA and protein-protein interactions etc. All these sites may be instrumental to “fine or coarse” tuning of gene expression.
• 4.4. The exact mechanisms by which changes in intracellular ionic environment are transduced, directly or indirectly, into alterations of the activity of trans-acting factors have not yet been fully uncovered. Changes in the degree of phosphorylation of regulatory proteins and/or of trans -acting factors may provoke fine tuning effects on cell type specific gene expression activity.
• 5.5. The intranuclear ionic environment is difficult to measure in an exact way. It can be influenced in a number of ways. The location of a gene, as determined by the position of the nucleus in the cytoplasm and by the association of chromatin to the nuclear matrix may be especially important in cells which can generate some type of intracellular gradient or in excitable cells.
• 6.6. In some somatic cell types—germinal vesicles may behave differently—the intranuclear inorganic ionic “environment” has been reported to be distinct from the cytoplasmic one. This challenges the widespread assumption that the nuclear envelope is always freely permeable to small molecules and inorganic ions.
• 7.7. It can be expected that the fast progress in the cloning of “electrically” controlled genes, in the identification of trans-acting factors, in their mode of interaction with genes and in the precise localization of genes within the nucleus may soon lead to substantial progress in this domain.

     

Isolation and polymerization of brain actin

The studies presented here confirm earlier reports that an actin-like protein is abundant in brain. However, when the traditional procedures for isolating muscle actin are applied to brain, many different proteins are extracted. Tubulin, a major protein in brain with properties similar to actin, is the major constituent. A method is described for isolating the “brain actin” to a purity of 90–95%. The isolation method begins with an extraction of bovine brain in low ionic strength buffer with ATP and sucrose. The extract is treated with NH₄SO₄, MgCl, and KCl and incubated at 37°C. A precipitate is formed which contains primarily tubulin and brain actin. Resolubilization of the brain actin is achieved with a low ionic strength buffer solution with sucrose and ATP. Further purification is accomplished by a cycle of polymerization—depolymerization. This “brain actin” shares with muscle actin the following properties: (1) Similar molecular weight and molecular charge as determined by SDS polyacrylamide gel and ordinary disc electrophoresis; (2) Polymerization to a filamentous form under the same conditions; (3) Contains 3-methylhistidine; (4) Vinblastine sulfate will induce filament formation.     

Aggregates and other particles as the origin of the “extraordinary” diffusional phase in polyelectrolyte solutions

The “extraordinary” diffusional phase (EP) at low ionic strength, and the conditions for 1 its removability by filtration were investigated for dilute solutions of the following linear polyelectrolytes: poly(L -lysine), heparin, chondroitin-6-sulfate, hyaluronate, polystyrene sulfonate, and variably ionized polyacrylamide. The EP was not present for all the different types studied, and for heparin, for example, the phase was present only for samples from certain sources. In all cases the phase was removable by filtration through sufficiently small pore-size membranes. Once filtered, the EP remained absent for over one week. It is concluded that the extraordinary diffusional phase consists of fairly stable polyelectrolyte aggregates, and sometimes also includes other very small particulate impurities. These aggregates and other small particles are thought to be present, or at least nascent, in the dry polyelectrolyte material, so that their properties may depend critically on the manner in which such dry material is produced. Tests for “reversibility” of the EP by cycling between high and low C_s by dialysis further confirm these conclusions. The evidence is thus against the EP representing any type of temporal aggregates or local ordering, at least for the linear polyelectrolytes studied in this work Rather, due to the extremely feeble scattering of ordinary polyelectrolytes at low ionic strength, the weak scattering from residual aggregates and other particles, not removed by ordinary filtration and centrifugation procedures, give autocorrelable scattering signals with long decay times. The “loss” of the extraordinary phase as ionic strength increases appears to be due simply to the weak EP scattering signal getting buried in the sharply increasing scattering from the ordinary polyelectrolyte phase. Model calculations based on experimental data support this latter conclusion. © 1992 John Wiley & Sons, Inc.     

Properties of (Mg2+ + Ca2+)-ATPase of erythrocyte membranes prepared by different procedures: Influence of Mg2+, Ca2+, ATP,and protein activator

Erythrocyte membranes prepared by three different procedures showed (Mg²⁺ + Ca²⁺)-ATPase activities differing in specific activity and in affinity for Ca²⁺. The (Mg²⁺ + Ca²⁺)-ATPase activity of the three preparations was stimulated to different extents by a Ca²⁺-dependent protein activator isolated from hemolystes. The Ca²⁺ affinity of the two most active preparations was decreased as the ATP concentration in the assay medium was increased. Lowering the ATP concentration from 2 mM to 2–200 μM or lowering the Mg:ATP ratio to less than one shifted the (Mg²⁺ + Ca²⁺)-ATPase activity in stepwise hemolysis membranes from mixed “high” and “low” affinity to a single high Ca²⁺ affinity. Membranes from which soluble proteins were extracted by EDTA (0.1 mM) in low ionic strengh, or membranes prepared by the EDTA (1–10 mM) procedure, did not undergo the shift in the Ca²⁺ affinity with changes in ATP and MgCl₂ concentrations. The EDTA-wash membranes were only weakly activated by the protein activator. It is suggested that the differences in properties of the (Mg²⁺ + Ca²⁺)-ATPase prepared by these three procedures reflect differences determined in part by the degree of association of the membrane with a soluble protein activator and changes in the state of the enzyme to a less activatable form.     

Effect of pH and ionic strength on the cytolytic toxin Cyt1A: a fluorescence spectroscopy study

Cyt1A is a cytolytic toxin produced by Bacillus thuringiensis var. israelensis. Due to its toxicity in vivo against mosquitoes and black flies, it is used as an environmentally friendly insecticide, although its mode of action is not completely understood. The toxin is membrane-active, but its membrane-bound conformation is unknown. In the absence of direct structural data, fluorescence spectroscopy was used to obtain indirect information on Cyt1A conformation changes in the environment mimicking the vicinity of the lipid membrane (lower pH and increased ionic strength). With decreasing pH, Cyt1A's surface hydrophobicity increased, which is consistent with an increased interaction with model membranes at low pH values, as observed previously. The pK(a) value of this conformation change is 4.4+/-0.1. Intrinsic tryptophan fluorescence decreased with decreasing pH, and the pK(a) value was the same as the one determined with synthetic probes. The protein has two types of hydrophobic binding sites, and at low pH these sites bind more probe molecules (bis-ANS) with a higher affinity than at pH 7.4. When bound to the lipid, the toxin exhibited conformation similar to the molten-globule state and showed some characteristics also observed at low pH. However, the conformation of the lipid-bound toxin did not depend on pH. Neutral salts like NaCl and KCl induced conformational changes at neutral pH, but not at low pH. These changes were most probably due to specific interactions of the salt ions with the charged amino acids on the protein surface rather than due to general effects such as Hofmeister and Debye-Hückel. Our results might contribute to elucidating the mode of action of Cyt1A, and perhaps also to improving the formulation of the insecticidal preparations.     

Factors Influencing Conformation Changes in a 7S Protein of Soybean Globulins by Ultracentrifugal Investigations

Effects of pH, ionic strength, kind of salts and disulfide bond cleaving agent (2-mercaptoethanol) on conformation changes revealed on ultracentrifugal patterns of a 7S protein in soybean globulins were investigated. In the solution with lower pH than isoelectric point, this protein dissociated into two components in low ionic strength, but showed a 7S sedimentation pattern in higher ionic strength than 0.1. On the other hand, in the solution with higher pH than isoelectric point, this protoin showed aggregation to a 9S isomer in lower ionic strength than 0.1. Between ionic strength of 0.1 and 0.5, the mixture of 7S and 9S forms existed and in higher ionic strength than 0.5, the protein kept a 7S form stablely. These reactions were reversible and effect of 2-mercaptoethanol was scarcely observed but those of salts were observed.

The molecular weight of the 9S isomer was approximately 370,000 and the s_20,w value was 12.30S. Therefore, the 9S isomer was considered to be a dimer of the 7S protein.     

Modulation of serotonin receptors by specific phosphatidylcholines

Treatment of mouse cortical brain membranes with dioleoylphosphatidylcholine produced a large (50%) decrease in serotonin binding sites. The time course for this effect paralleled an increase in oleic acid in membrane phosphatidycholine and an increase in membrane fluidity. “Active Lipid” produced a similar decrease in serotonin binding sites, while fluidizing the membranes even more strongly. Distearoylphosphatidylcholine had no effect on serotonin binding sites or membrane fluidity by itself, but was capable of counteracting both the reduction in binding sites and membrane fluidity produced by “Active Lipid”. The data indicate that specific phosphatidylcholines can have profound effects on serotonin receptors, but a clear picture of the relative importance of membrane fluidity per se versus more specific phospholipid effects will require further investigation.