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dc.contributor.authorIrnaten, Mustapha
dc.contributor.authorBarry, Richard C
dc.contributor.authorQuill, Barry
dc.contributor.authorClark, Abbot F
dc.contributor.authorHarvey, Brian J P
dc.contributor.authorO'Brien, Colm J
dc.date.accessioned2011-04-07T10:58:18Z
dc.date.available2011-04-07T10:58:18Z
dc.date.issued2009-01
dc.identifier.citationActivation of stretch-activated channels and maxi-K+ channels by membrane stress of human lamina cribrosa cells. 2009, 50 (1):194-202 Invest. Ophthalmol. Vis. Sci.en
dc.identifier.issn1552-5783
dc.identifier.pmid18775862
dc.identifier.doi10.1167/iovs.08-1937
dc.identifier.urihttp://hdl.handle.net/10147/127658
dc.description.abstractThe lamina cribrosa (LC) region of the optic nerve head is considered the primary site of damage in glaucomatous optic neuropathy. Resident LC cells have a profibrotic potential when exposed to cyclical stretch. However, the mechanosensitive mechanisms of these cells remain unknown. Here the authors investigated the effects of membrane stretch on cell volume change and ion channel activity and examined the associated changes in intracellular calcium ([Ca(2+)](i)).
dc.description.abstractThe authors used primary LC cells obtained from normal human donor eyes. Confocal microscopy was used to investigate the effect of hypotonic cell membrane stretch on cell volume changes. Whole-cell patch-clamp and calcium imaging techniques were used to investigate the effect of hypotonicity on ion channel(s) activity and [Ca(2+)](i) changes, respectively. RT-PCR was used to examine for the maxi-K(+) signature in LC cells.
dc.description.abstractIn this study, LC cells showed significant volume changes in response to hypotonic cell swelling. The authors characterized a large conductance K(+) channel (maxi-K(+)) in LC cells and demonstrated its increased activity during cell membrane hypotonic stretch. RT-PCR revealed the presence of maxi-K(+) signature in LC cells. The authors showed the [Ca(2+)](i) and maxi-K(+) channels to be dependent on extracellular Ca(2+) and inhibited by gadolinium, which blocks stretch-activated channels (SACs). Pretreatment with thapsigargin, which blocks the release of Ca(2+) from endoplasmic reticulum stores, showed no significant difference in [Ca(2+)](i) concentration on hypotonic swelling.
dc.description.abstractThe results show that hypotonic stress of human LC cells activates SAC and Ca(2+)-dependent maxi-K(+) channels and that the increase in [Ca(2+)](i) during cell swelling was predominantly from extracellular sources (or intracellular stores other than the endoplasmic reticulum). These findings improve the understanding of how LC cells respond to cell membrane stretch. Further experiments in this area may reveal future targets for novel therapeutic intervention in the management of glaucoma.
dc.language.isoenen
dc.relation.urlhttp://www.iovs.org/content/50/1/194.full.pdf+htmlen
dc.subject.meshBiological Markers
dc.subject.meshCalcium
dc.subject.meshCell Culture Techniques
dc.subject.meshCell Membrane
dc.subject.meshCell Size
dc.subject.meshDNA Primers
dc.subject.meshGadolinium
dc.subject.meshHumans
dc.subject.meshHypotonic Solutions
dc.subject.meshIon Channels
dc.subject.meshLarge-Conductance Calcium-Activated Potassium Channel alpha Subunits
dc.subject.meshLarge-Conductance Calcium-Activated Potassium Channels
dc.subject.meshMale
dc.subject.meshMicroscopy, Confocal
dc.subject.meshOptic Disk
dc.subject.meshPatch-Clamp Techniques
dc.subject.meshPeptides
dc.subject.meshRNA, Messenger
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction
dc.subject.meshScorpion Venoms
dc.subject.meshStress, Physiological
dc.subject.meshThapsigargin
dc.titleActivation of stretch-activated channels and maxi-K+ channels by membrane stress of human lamina cribrosa cells.en
dc.typeArticleen
dc.contributor.departmentMolecular Medicine Laboratories, RCSI Education and Research Centre, Beaumont Hospital, Dublin, Ireland. irnatenm@yahoo.fren
dc.identifier.journalInvestigative ophthalmology & visual scienceen
dc.description.provinceLeinster
html.description.abstractThe lamina cribrosa (LC) region of the optic nerve head is considered the primary site of damage in glaucomatous optic neuropathy. Resident LC cells have a profibrotic potential when exposed to cyclical stretch. However, the mechanosensitive mechanisms of these cells remain unknown. Here the authors investigated the effects of membrane stretch on cell volume change and ion channel activity and examined the associated changes in intracellular calcium ([Ca(2+)](i)).
html.description.abstractThe authors used primary LC cells obtained from normal human donor eyes. Confocal microscopy was used to investigate the effect of hypotonic cell membrane stretch on cell volume changes. Whole-cell patch-clamp and calcium imaging techniques were used to investigate the effect of hypotonicity on ion channel(s) activity and [Ca(2+)](i) changes, respectively. RT-PCR was used to examine for the maxi-K(+) signature in LC cells.
html.description.abstractIn this study, LC cells showed significant volume changes in response to hypotonic cell swelling. The authors characterized a large conductance K(+) channel (maxi-K(+)) in LC cells and demonstrated its increased activity during cell membrane hypotonic stretch. RT-PCR revealed the presence of maxi-K(+) signature in LC cells. The authors showed the [Ca(2+)](i) and maxi-K(+) channels to be dependent on extracellular Ca(2+) and inhibited by gadolinium, which blocks stretch-activated channels (SACs). Pretreatment with thapsigargin, which blocks the release of Ca(2+) from endoplasmic reticulum stores, showed no significant difference in [Ca(2+)](i) concentration on hypotonic swelling.
html.description.abstractThe results show that hypotonic stress of human LC cells activates SAC and Ca(2+)-dependent maxi-K(+) channels and that the increase in [Ca(2+)](i) during cell swelling was predominantly from extracellular sources (or intracellular stores other than the endoplasmic reticulum). These findings improve the understanding of how LC cells respond to cell membrane stretch. Further experiments in this area may reveal future targets for novel therapeutic intervention in the management of glaucoma.


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