CHANNEL-TYPE MOLECULAR-STRUCTURES .4. TRANSMEMBRANE TRANSPORT OF ALKALI-METAL IONS BY BOUQUET MOLECULES

This report describes transport experiments with 'bouquet' molecules d esigned to act as artificial ion channels. The 'bouquets' are based on a central macrocycle which is either an 18-crown-6 (B-M) or a cyclode xtrin derivative (B-CD) to which are attached poly(ethylene oxide) [po ly(oxyethylene)] chains (B-M(o) and B-CD(o)) or polyalkyl chains (B-M( c) and B-CD(c)) tipped with carboxylate end-groups. The 'bouquets' wer e studied in liposomes prepared from egg phosphatidylcholine (egg PC), dipalmitoyl phosphatidylcholine (DPPC) and a mixture of egg PC, stear ylamine and cholesterol. Opposing gradients in Li+ and Na+ concentrati on were created and the transport of alkali-metal ions down their conc entration gradients was followed directly by Li-7 and Na-23 NMR spectr oscopy. 'Bouquets' were found to cause a one-for-one exchange of Na+ f or Li+ (antiport). In order to estimate transport rates, the extent of Na+ entry into liposomes was followed as a function of time. All 'bou quets' transported ions at similar rates in fluid membranes. Compariso n of transport rates in fluid- (egg PC) and gel-state membranes (DPPC) was used to distinguish carrier and channel mechanisms. Control exper iments demonstrated that a known carrier (monensin A) gave significant ly lower transport rates in gel-state membranes. Two 'bouquets', B-M(c ) and B-CD(o), were found to transport Na+ at similar rates in fluid- and gel-state membranes; this suggests that ion passage occurs prefere ntially by the channel mechanism and not by the carrier mechanism. Var iation of transport rate with 'bouquet' concentration was probed for B -M(o) and B-M(c) and the rates were found to increase with B-M(c) conc entration but not with B-M(o) concentration. Since the transport rate is expected to be proportional to transporter concentration in both th e carrier and channel mechanisms, this indicates that B-M(o) uses neit her a carrier nor a channel mechanism. The mechanism by which 'bouquet ' molecules operate and the criteria which may be used to decide wheth er functioning channels have been created are discussed.