title: Transport properties of the calcium ionophore ETH-129.
abstract: The transport mechanism and specificities of ionophore ETH-29 have been investigated in a highly defined phospholipid vesicle system, with the goal of facilitating the application of this compound to biological problems. ETH-129 transports Ca(2+) via an electrogenic mechanism, in contrast to A23187 and ionomycin, which function in a charge neutral manner. The rate of transport is a function of membrane potential, increasing by 3.9-fold per 59 mV over a broad range of that parameter. Rate is independent of the transmembrane pH gradient and strongly stimulated by the uncoupler carbonyl cyanide m-chlorophenylhydrazone when no external potential has been applied. The effect of uncoupler reflects the collapse of an opposing potential arising during Ca(2+) transport, but also reflects the formation of a mixed complex between the uncoupler, ETH-129, and Ca(2+) that readily permeates the vesicle membrane. Oleate does not substitute for the uncoupler in either regard. ETH-129 transports polyvalent cations according to the selectivity sequence La(3+) > Ca(2+) > Zn(2+) approximately equal to Sr(2+) > Co(2+) approximately equal to Ni(2+) approximately equal to Mn(2+), with the magnitude of the selectivity coefficients reflecting the cation concentration range considered. There is little or no activity for the transport of Na(+), K(+), and Mg(2+). These properties suggest that ETH-129 will be useful for investigating the consequences of a mitochondrial Ca(2+) overload in mammalian cells, which is difficult to pursue through the application of electroneutral ionophores.
authors.affiliation: Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: E
authors.initials: E
authors.lastname: Wang
authors.forename: W L
authors.initials: WL
authors.lastname: Erdahl
authors.forename: S A
authors.initials: SA
authors.lastname: Hamidinia
authors.forename: C J
authors.initials: CJ
authors.lastname: Chapman
authors.forename: R W
authors.initials: RW
authors.lastname: Taylor
authors.forename: D R
authors.initials: DR
authors.lastname: Pfeiffer
mesh_terms: D001692:Biological Transport; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002412:Cations; D003510:Cyclohexanes / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors; D006835:Hydrazones / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000737:chemistry* / Q000494:pharmacology*; D007477:Ions; D007700:Kinetics; D008564:Membrane Potentials; D008956:Models, Chemical; D010743:Phospholipids / Q000737:chemistry; D011188:Potassium / Q000737:chemistry; D021381:Protein Transport; D013997:Time Factors
chemical_list: D002412:Cations; D003510:Cyclohexanes; D004791:Enzyme Inhibitors; D006835:Hydrazones; D007476:Ionophores; D007477:Ions; D010743:Phospholipids; C070053:carbonyl 3-chlorophenylhydrazone; D000001:Calcimycin; D015759:Ionomycin; C077946:N,N,N',N'-tetracyclohexyl-3-oxapentanediamide; D011188:Potassium; D002118:Calcium