Elevated maxi-K+ ion channel current in glaucomatous lamina cribrosa cells

Mustapha Irnaten, Richard C. Barry, Deborah M. Wallace, Neil G. Docherty, Barry Quill, Abbot F. Clark, Colm J. O'Brien

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

The connective tissue plates of the lamina cribrosa (LC) region are continuously exposed to a mechanically dynamic environment. To study how the LC cells respond to these mechanical forces, we measured the mechano-sensitive calcium dependent maxi-K+ ion channel current in the cell membrane of LC cells of glaucoma and normal subjects. Primary culture LC cells from 7 normal and 7 age matched glaucoma donors were studied. Perfusion of cells with hypotonic solution was used to stretch the cell membrane. Whole-cell patch-clamp technique was used to measure the basal (non stretched) and hypotonic stretch-induced changes in maxi-K+ ion channel activity in normal and glaucoma LC cells. The role of membrane-type Ca2+ entry channel inhibition (verapamil) and internal Ca2+ store re-uptake blockade (2-APB) on maxi-K+ activity was also examined. Basal and stretched-induced maxi-K+ current were significantly elevated in the glaucoma LC cells compared to normal controls (p<0.05). In normal LC cells hypotonic stretch elevated the mean maxi-K+ current from 18.5±5.7pA/pF (at Vp=+100mV) to 88.4±12.4pA/pF (P<0.05), and from 39.5±7.3pA/pF to 133.1±18.5pA/pF in glaucoma LC cells (P<0.02). Verapamil and 2-APB significantly reduced basal maxi-K+ current in glaucoma LC cells (33.1±8.2pA/pF to 17.9±5.6pA/pF; and 32.2±8.3pA/pF to 17.3±5.4pA/pF, P<0.05, respectively) but not in normal LC cells (P>0.05). Following hypotonic stretch, verapamil and 2-APB significantly (P<0.05) reduced the maxi-K+ current in both normal and glaucoma LC cells. Baseline and hypotonic stretch induced Ca2+-dependent maxi-K+ channel activity are elevated in LC cells of glaucoma patients, which may result from the abnormally high levels of intracellular calcium in glaucoma LC cells.

Original languageEnglish
Pages (from-to)224-229
Number of pages6
JournalExperimental eye research
Volume115
DOIs
StatePublished - Oct 2013

Keywords

  • Fibrosis
  • Glaucoma
  • Lamina cribrosa
  • Maxi-k

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    Irnaten, M., Barry, R. C., Wallace, D. M., Docherty, N. G., Quill, B., Clark, A. F., & O'Brien, C. J. (2013). Elevated maxi-K+ ion channel current in glaucomatous lamina cribrosa cells. Experimental eye research, 115, 224-229. https://doi.org/10.1016/j.exer.2013.07.022