Irreversible and reversible pore formation by polymeric alkylpyridinium salts (poly-APS) from the sponge Reniera sarai

Br J Pharmacol. 2003 Aug;139(8):1399-408. doi: 10.1038/sj.bjp.0705374.


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 approximately 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 micro g ml(-1)) was applied to cultured dorsal root ganglion neurones or HEK 293 cells and changes in cell membrane properties were measured using whole-cell patch-clamp recording and fura-2 Ca(2+) imaging. 2. Poly-APS (50 micro g ml(-1)) evoked irreversible depolarisations in membrane potential and reductions in input resistance. However, doses of 5 micro g ml(-1) and less produced reversible effects on these cell membrane characteristics and on Ca(2+) permeability. 3. At 0.05 micro g ml(-1), poly-APS could robust transient increases in Ca(2+) permeability without damaging the neurones or subsequently attenuating Ca(2+) entry through voltage-activated channels. 4. Bathing cells in NaCl-based extracellular medium containing 1.5 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 Ca(2+) 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 poly-APS and cell membranes could be attenuated by zinc.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cell Line
  • Cell Membrane / drug effects*
  • Cell Membrane / metabolism
  • Cell Membrane / physiology
  • Cell Membrane Permeability / drug effects
  • Dose-Response Relationship, Drug
  • Ganglia, Spinal / cytology
  • Humans
  • Kidney / cytology
  • Kidney / embryology
  • Membrane Potentials / drug effects
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / physiology
  • Patch-Clamp Techniques
  • Polymers / isolation & purification
  • Polymers / pharmacology*
  • Porifera / chemistry*
  • Pyridinium Compounds / isolation & purification
  • Pyridinium Compounds / pharmacology*
  • Rats
  • Zinc / pharmacology


  • Polymers
  • Pyridinium Compounds
  • poly-APS
  • Zinc
  • Calcium