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

David McClelland, R. M. Evans, I. Abidin, S. Sharma, F. Z. Choudhry, Marcel Jaspars, K. Sepcic, Roderick Hamilton Scott

Research output: Contribution to journalArticle

20 Citations (Scopus)

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 similar to19 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 mug 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 Ca2+ imaging.

2 Poly-APS (50 mug ml(-1)) evoked irreversible depolarisations in membrane potential and reductions in input resistance. However, doses of 5 mug ml(-1) and less produced reversible effects on these cell membrane characteristics and on Ca2+ permeability.

3 At 0.05 mug ml(-1), poly-APS could evoke robust transient increases in Ca2+ permeability without damaging the neurones or subsequently attenuating Ca2+ 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 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 poly-APS and cell membranes could be attenuated by zinc.

Original languageEnglish
Pages (from-to)1399-1408
Number of pages9
JournalBritish Journal of Pharmacology
Volume139
Issue number8
DOIs
Publication statusPublished - Jul 2003

Keywords

  • pore former
  • sponge toxin
  • polymeric alkylpyridinium salt
  • halitoxins
  • intracellular calcium
  • sensory neurone
  • CALCIUM-CHANNEL CURRENTS
  • 3-ALKYLPYRIDINIUM POLYMERS
  • AMPHIMEDON VIRIDIS
  • HALICLONA-VIRIDIS
  • HALITOXIN
  • MEMBRANE
  • NEURONS
  • CELLS

Cite this

Irreversible and reversible pore formation by polymeric alkylpyridinium salts (poly-APS) from the sponge Reniera sarai. / McClelland, David; Evans, R. M.; Abidin, I.; Sharma, S.; Choudhry, F. Z.; Jaspars, Marcel; Sepcic, K.; Scott, Roderick Hamilton.

In: British Journal of Pharmacology, Vol. 139, No. 8, 07.2003, p. 1399-1408.

Research output: Contribution to journalArticle

McClelland, David ; Evans, R. M. ; Abidin, I. ; Sharma, S. ; Choudhry, F. Z. ; Jaspars, Marcel ; Sepcic, K. ; Scott, Roderick Hamilton. / Irreversible and reversible pore formation by polymeric alkylpyridinium salts (poly-APS) from the sponge Reniera sarai. In: British Journal of Pharmacology. 2003 ; Vol. 139, No. 8. pp. 1399-1408.
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T1 - Irreversible and reversible pore formation by polymeric alkylpyridinium salts (poly-APS) from the sponge Reniera sarai

AU - McClelland, David

AU - Evans, R. M.

AU - Abidin, I.

AU - Sharma, S.

AU - Choudhry, F. Z.

AU - Jaspars, Marcel

AU - Sepcic, K.

AU - Scott, Roderick Hamilton

PY - 2003/7

Y1 - 2003/7

N2 - 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 similar to19 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 mug 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 Ca2+ imaging.2 Poly-APS (50 mug ml(-1)) evoked irreversible depolarisations in membrane potential and reductions in input resistance. However, doses of 5 mug ml(-1) and less produced reversible effects on these cell membrane characteristics and on Ca2+ permeability.3 At 0.05 mug ml(-1), poly-APS could evoke robust transient increases in Ca2+ permeability without damaging the neurones or subsequently attenuating Ca2+ 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 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 poly-APS and cell membranes could be attenuated by zinc.

AB - 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 similar to19 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 mug 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 Ca2+ imaging.2 Poly-APS (50 mug ml(-1)) evoked irreversible depolarisations in membrane potential and reductions in input resistance. However, doses of 5 mug ml(-1) and less produced reversible effects on these cell membrane characteristics and on Ca2+ permeability.3 At 0.05 mug ml(-1), poly-APS could evoke robust transient increases in Ca2+ permeability without damaging the neurones or subsequently attenuating Ca2+ 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 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 poly-APS and cell membranes could be attenuated by zinc.

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KW - sensory neurone

KW - CALCIUM-CHANNEL CURRENTS

KW - 3-ALKYLPYRIDINIUM POLYMERS

KW - AMPHIMEDON VIRIDIS

KW - HALICLONA-VIRIDIS

KW - HALITOXIN

KW - MEMBRANE

KW - NEURONS

KW - CELLS

U2 - 10.1038/sj.bjp.0705374

DO - 10.1038/sj.bjp.0705374

M3 - Article

VL - 139

SP - 1399

EP - 1408

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

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ER -