Ion transport across thin lipid membranes: a critical discussion of mechanisms in selected systems

Haydon, D. A.; Hladky, Stephen B.

doi:10.1017/s0033583500000883

Cited by 425 publications

(202 citation statements)

References 101 publications

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“…Small step increases in current corresponding to conductance increases of about 10-11 mho are apparent in this record. Similar discrete conductance changes have been seen in bilayer membranes in the presence of antibiotics for which there is good evidence that pores form in the membranes (15,16). These have been interpreted as the opening of individual channels.…”

Section: Resultssupporting

confidence: 60%

Interaction of lymphocytes with lipid bilayer membranes: a model for lymphocyte-mediated lysis of target cells.

Henkart¹,

Blumenthal²

1975

Proc. Natl. Acad. Sci. U.S.A.

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Horizontal li id bilayer membranes were used as a model system to study lymphocyte-mediated killing of target cells. Dinitrophenylated lipid bilayers can physically support dozens of lymphocytes for periods of over one hour without breakage or increasing the electrical conductance of the membrane. However, in the presence of antibody against Dnp, human lymphocytes rapidly induced increases in membrane conductance of several orders of magnitude without membrane breakage. Such ionic permeability increases occurred only when the membrane voltage was positive on the lymphocyte side, as would be the case with a target cell membrane. The lymphocyte and antibody dependence of this conductance increase parallels that observed for lymphocyte killing of antibody-coated target cells. The results are interpreted as evidence that the primary event in lymphocyte kiling of antibody-coated target cells is the creation of ion-conducting channels in the target membrane. Lymphocytes appear to play a major role in the immunologic rejection of foreign grafts and tumors. Since lymphocytes have also been shown to be able to destroy such foreign cells directly in vitro, interest has focused on the mechanism of this lymphocyte-induced killing (1). Several lines of evidence suggest that lymphocytes destroy their target cells by inducing a breakdown in the permeability barrier to small ions, leading to a subsequent colloid osmotic lysis. Morphological studies of the killing reactions have demonstrated that the cytolytic process is accompanied by a marked swelling of the dying cell (2). The study of target cells internally labeled with molecules of different sizes shows that the smaller molecules are released from the dying cell faster than those of high molecular weight (3-5). High concentrations of macromolecules have been shown to suppress the final release of 51Cr from the target cell (5, 6), but the interpretation of these findings is controversial (7). There has been no evidence to indicate whether the early permeability increase in the target membrane is caused directly by the attacking lymphocyte or is a secondary consequence of some other primary injury.In order to study the ability of lymphocytes to induce permeability changes in a foreign membrane, we have studied the interaction of human lymphocytes with artificial lipid bilayer membranes. Such "black lipid membranes" have been used extensively to model the permeability properties of naturally occurring membranes and have been especially useful in studying the properties of membrane active drugs (8,9). The ionic permeability of such membranes can conveniently be studied by electrical measurements. In the present studies we have used an antigenic lipid to form a bilayer membrane, and have examined the ability of nonimmune lymphocytes to induce permeability changes in the presence of antibody bound to the membrane. This system is a model for the antibody-dependent (but complement-independent) killing of target cells mediated (10). Dnp-phosphatidylethanolamine (Dnp-PE) ...

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Section: Resultssupporting

confidence: 60%

Interaction of lymphocytes with lipid bilayer membranes: a model for lymphocyte-mediated lysis of target cells.

Henkart¹,

Blumenthal²

1975

Proc. Natl. Acad. Sci. U.S.A.

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“…The inclusion of TPB enhances the equilibration of [3H]-TPP between the inside and outside of the cell. This is thought to result from the uptake of TPB into the lipid membrane which has a preference for negatively charged ions such as TPB (Haydon & Hladky, 1972). The uptake of TPB results in a more favourable environment for positively charged ions, such as TPP, to cross.…”

Section: The Antagonism Displayed By the Quaternary Ionsmentioning

confidence: 99%

Antagonism by lipophilic quaternary ions of the K⁺ channel opener, levcromakalim, in vascular smooth muscle

McPherson

Piekarska

1994

British J Pharmacology

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1 The aim of this study was to characterize the interaction between the K+ channel opener levcromakalim (LKM) and several quaternary ions, in vascular smooth muscle, in vitro. Segments of isolated, thoracic aorta of the rat were suspended in organ baths filled with Krebs solution at 37C. Cumulative concentration-response curves to LKM were obtained in the absence and in the presence of increasing concentrations of quaternary ions using a number of agents to pre-constrict the vessel. The ions tested were tetraphenylphosphonium (chloride TPP-C1 and bromide TPP-Br salts), tetrapentylammonium (TPeA), tetraethylammonium (TEA), tetraphenylarsonium (TPAs) and tetraphenylboron (TPB). 2 For the compounds which antagonized the vasorelaxation responses of LKM, 'apparent pKB' values were estimated on the basis of a single concentration of antagonist. These were then used to obtain the following order of potency: TPP-Br (7.22 ± 0.25) = TPAs (7.12 ± 0.04) = TPP-Cl (7.11 ± 0.15) > TPeA (6.23 ± 0.20). TEA and TPB were both found to be inactive at the maximum concentrations used. 3 The interaction between the cationic TPP and anionic TPB was also investigated. The shift in the LKM concentration-response curve constructed in the presence of both of these compounds was compared to that when each agent was present separately. We found that TPB, at concentrations greater than 1 gLM, reversed the blockade of the LKM-mediated relaxation induced by TPP (3 IsM). 4 Similar experiments were undertaken combining TPB with either alinidine or glibenclamide (both functional antagonists of K+ channel openers). It was found that TPB (10 gM) partially reversed the antagonism induced by alinidine (30 and 100 gM) but had no effect on the action of glibenclamide (3 gM). 5These studies show that lipophilic cations such as TPP and TPAs are potent antagonists of levcromakalim-mediated vasorelaxation responses in the rat thoracic aorta. The mechanism by which these compounds cause their antagonism is not known. However, given the lipophilicity of these compounds, it is possible they may act at a number of sites including the KATP channel itself or possibly via some other intracellular mechanism.

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“…The polypeptide antibiotic gramicidin A induces an ionic conductance in planar bilayers by forming pores of helical structure (17). Fig.…”

mentioning

confidence: 99%

Lipid phase transition in planar bilayer membrane and its effect on carrier- and pore-mediated ion transport.

Boheim¹,

Hanke²,

Eibl³

1980

Proc. Natl. Acad. Sci. U.S.A.

127

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Using mixed-chain lipids, we have recorded cooling and heating curves of planar bilayer membranes while they passed the lipid phase transition range. With unmodified planar bilayers, spontaneous current fluctuations are observed near the lipid phase transition temperature (tc t 290C). This effect coincides with the expected and measured decrease in membrane capacitance. Carrier (valinomycin)-modified planar bilayers exhibit near tc an abrupt change from a high-conducting state above tc to the state ofbare membrane conductance below tc. In contrast to this behavior, planar bilayers modified by pore-forming antibiotics (gramicidin A, alamethicin) do not show any peculiar effect at tc. However, at 22-230C a pronounced maximum in pore-induced conductance is seen. Whereas the gramicidin A pore abruptly stops stepwise fluctuations below 16'C, with alamethicin a few long-lasting pore and pore state fluctuations persist down to 10'C. It is suggested that the carrier may freeze out into the membrane/water interface. The effects observed with pore-forming substances, on the other hand, are interpreted in terms of lateral phase separation into pure lipid and lipid/antibiotic domains. Phase changes are well-known phenomena in artificial lipid/ water systems (1) and biological systems (2). These phase transitions, which may play a role in triggering biological processes (3), can be induced by temperature changes or by interaction of ions with charged membrane lipids (4, 5). A great number of publications report on phase transition phenomena in pure and protein-loaded vesicles and liposomes. Due to the instability of planar bilayer membranes in the solid state, there are so far only two reports on electrochemical measurements in the freezing and melting range of planar lipid bilayer membranes. Experiments carried out on membranes from a 1:1 (wt/wt) mixture of dipalmitoylglycerol and distearoylglycerol in n-decane led to the interpretation that ion carriers became frozen and thus immobile within the membrane phase (6). On the other hand, the ionic conductance induced by the pore-former gramicidin was found to remain unchanged at the transition temperature tc of 41'C. Recently, ion-conducting channels were reported to appear in unmodified planar bilayer membranes at the phase tr of 59°C (7). Membranes were formed from a 1,2-distearoyl-glycero-3-phosphocholine/decane solution. There is also a paper, based on optical reflectivity measurements on membranes from monostearoylglycerol in n-hexadecane, which demonstrated an ;70% increase in membrane thickness when the system was cooled below the tc of 55°C (8).Using saturated mixed-chain lipids with a tc of ;290C, we succeeded in forming virtually solvent-free planar bilayer membranes below and above tc. In this paper we report our investigations on pure and ionophore-modified planar bilayers of this type in the 10-40°C temperature range.

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Ion transport across thin lipid membranes: a critical discussion of mechanisms in selected systems

Cited by 425 publications

References 101 publications

Interaction of lymphocytes with lipid bilayer membranes: a model for lymphocyte-mediated lysis of target cells.

Interaction of lymphocytes with lipid bilayer membranes: a model for lymphocyte-mediated lysis of target cells.

Antagonism by lipophilic quaternary ions of the K⁺ channel opener, levcromakalim, in vascular smooth muscle

Lipid phase transition in planar bilayer membrane and its effect on carrier- and pore-mediated ion transport.

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Ion transport across thin lipid membranes: a critical discussion of mechanisms in selected systems

Cited by 425 publications

References 101 publications

Interaction of lymphocytes with lipid bilayer membranes: a model for lymphocyte-mediated lysis of target cells.

Interaction of lymphocytes with lipid bilayer membranes: a model for lymphocyte-mediated lysis of target cells.

Antagonism by lipophilic quaternary ions of the K+ channel opener, levcromakalim, in vascular smooth muscle

Lipid phase transition in planar bilayer membrane and its effect on carrier- and pore-mediated ion transport.

Contact Info

Product

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Antagonism by lipophilic quaternary ions of the K⁺ channel opener, levcromakalim, in vascular smooth muscle