| Author/Editor | McClelland, D; Evans, RM; Abidin, I; Sharma, S; Choudhry, FZ; Jaspars, M; Sepčić, K; Scott, RH | |
| Title | Irreversible and reversible pore formation by polymeric alkylpyridinium salts (poly-APS) from the sponge Reneira sarai | |
| Type | članek | |
| Source | Br J Pharmacol | |
| Vol. and No. | Letnik 139, št. 8 | |
| Publication year | 2003 | |
| Volume | str. 1399-408 | |
| Language | eng | |
| Abstract | 1 In this study, we investigated the electrophysiological actions of a high molecular weight fraction, predominantly containing two polymeric 1,3-alkylpyridinium salts (poly-APS) of 5.5 and ,..19 kDa isolated from the marine sponge Reniera sarai. The biological properties of poly-APS are of particular interest because this preparation may be used to deliver macromolecules into the intracellular environment without producing long-term damage to cells. Poly-APS (50-0.05 icgml-1) was applied to cultured dorsal root ganglion neuxones or HEK 293 cells and changes in cell membrane properties were measured using whole-cell patch-clamp recording and fura-2 Ca2+ imaging. 2 Poly-APS (50 ieg ml-1) evoked irreversible depolarisations in membrane potential and reductions in input resistance. However, doses of 5 microgml-1 and less produced reversible effects on these cell membrane characteristics and on Cap2+ pemeaneability. 3 At 0.05microg ml-1, poly-APS could evoke robust transient increases in Cax+ permeability without damaging the neurones or subsequently attenuating Ca2+ entry through voltage-activated channels. 4 Bathing cells in NaCI-based extracellular medium containing l.5 mM zinc attenuated the irreversible and reversible effects of poly-APS on membrane properties (membrane potential, input resistance and whole-cell currents). In both DRG neurones and HEK 293 cells, zinc attenuated Ca2+ entry evoked by poly-APS. These effects of zinc were only observed if zinc was continually present during poly APS application. However, zinc failed to attenuate the actions of poly-APS if it was applied after the sponge toxin preparation had evoked changes in membrane properties. 5 In conclusion, the pore-forming preparation poly-APS can have dose-dependent interactions with cell membranes and at low doses these can be reversible. Additionally, the interactions between polyAPS and cell membranes could be attenuated by zinc. | |
| Descriptors | PORIFERA PYRIDINIUM COMPOUNDS TOXINS CELL MEMBRANE PERMEABILITY CALCIUM GANGLIA PATCH-CLAMP TECHNIQUES |