Activation of stretch-activated channels and maxi-K+ channels by membrane stress of human lamina cribrosa cells.

Hdl Handle:
http://hdl.handle.net/10147/127658
Title:
Activation of stretch-activated channels and maxi-K+ channels by membrane stress of human lamina cribrosa cells.
Authors:
Irnaten, Mustapha; Barry, Richard C; Quill, Barry; Clark, Abbot F; Harvey, Brian J P; O'Brien, Colm J
Affiliation:
Molecular Medicine Laboratories, RCSI Education and Research Centre, Beaumont Hospital, Dublin, Ireland. irnatenm@yahoo.fr
Citation:
Activation 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.
Journal:
Investigative ophthalmology & visual science
Issue Date:
Jan-2009
URI:
http://hdl.handle.net/10147/127658
DOI:
10.1167/iovs.08-1937
PubMed ID:
18775862
Additional Links:
http://www.iovs.org/content/50/1/194.full.pdf+html
Abstract:
The 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)).; The 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.; In 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.; The 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.
Item Type:
Article
Language:
en
MeSH:
Biological Markers; Calcium; Cell Culture Techniques; Cell Membrane; Cell Size; DNA Primers; Gadolinium; Humans; Hypotonic Solutions; Ion Channels; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; Large-Conductance Calcium-Activated Potassium Channels; Male; Microscopy, Confocal; Optic Disk; Patch-Clamp Techniques; Peptides; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction; Scorpion Venoms; Stress, Physiological; Thapsigargin
ISSN:
1552-5783

Full metadata record

DC FieldValue Language
dc.contributor.authorIrnaten, Mustaphaen
dc.contributor.authorBarry, Richard Cen
dc.contributor.authorQuill, Barryen
dc.contributor.authorClark, Abbot Fen
dc.contributor.authorHarvey, Brian J Pen
dc.contributor.authorO'Brien, Colm Jen
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-

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