title: Effect of phloretin on ionophore mediated electroneutral transmembrane translocations of H(+), K(+) and Na(+) in phospholipid vesicles.
abstract: Rates of M(+)/H(+) exchange (M(+)=K(+), Na(+)) across phospholipid membranes by ionophore mediated electroneutral translocations and transports through channels could either increase or decrease or change negligibly on adding the polar molecule phloretin to the membrane. The changes depend on pH, the concentration and choice of M(+) and choice of ionophore/channel. Such diverse behaviours have been inferred from studies on the decay of the pH difference across soybean phospholipid vesicular membrane (=Delta pH). The transporters used in this study are (a) the exchange ionophores: nigericin, monensin; (b) combinations of alkali metal ion carriers, valinomycin or nonactin with weak acids carbonyl cyanide m-chlorophenylhydrazone or 2,4-dinitrophenol and (c) channels formed by gramicidin A. All the diverse results can be rationally explained if we take note of the following. (i) The rate limiting steps are associated with the transmembrane translocations involving the rate limiting species identified in the literature. (ii) Phloretin in the membrane decreases the apparent M(+) dissociation constant, K(M), of the M(+) bound ionophores/channels which has the effect of increasing the concentration of these species. (iii) The concentrations of H(+) bound ionophores/channels decrease on adding phloretin. (iv) Phloretin inhibits ternary complex formation (involving valinomycin or nonactin, M(+) and an anion) by forming 1:2 complexes with valinomycin-M(+) or nonactin-M(+). (v) On adding 6-ketocholestanol to the membrane (instead of phloretin) K(M) increases. The decreases/increases in K(M) mentioned above are consistent with the consequences of a hypothesis in which phloretin decreases and 6-ketocholestanol increases the positive internal membrane dipole potential.
authors.affiliation: Department of Electrical Engineering, Indian Institute of Technology, Bombay, Mumbai, India.
authors.forename: S
authors.initials: S
authors.lastname: Bala
authors.forename: M H
authors.initials: MH
authors.lastname: Kombrabail
authors.forename: B S
authors.initials: BS
authors.lastname: Prabhananda
mesh_terms: D006863:Hydrogen-Ion Concentration; D017136:Ion Transport / Q000187:drug effects*; D007476:Ionophores / Q000737:chemistry; D007653:Ketocholesterols / Q000494:pharmacology; D008051:Lipid Bilayers / Q000378:metabolism; D008564:Membrane Potentials; D008985:Monensin / Q000737:chemistry; D009550:Nigericin / Q000737:chemistry; D010693:Phloretin / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D011522:Protons; D012964:Sodium / Q000378:metabolism; D013025:Glycine max
chemical_list: D007476:Ionophores; D007653:Ketocholesterols; D008051:Lipid Bilayers; D010743:Phospholipids; D011522:Protons; C063833:6-ketocholestanol; D008985:Monensin; D012964:Sodium; D009550:Nigericin; D011188:Potassium; D010693:Phloretin