December 2002
Volume 43, Issue 13
ARVO Annual Meeting Abstract  |   December 2002
The Effects of Unoprostone on L-type Ca2+ Channels of Human Trabecular Meshwork Cells
Author Affiliations & Notes
  • M Wiederholt
    Inst Klin Physiologie Universitatsklinikum Ben Frkln Berlin Germany
  • K Steinhausen
    Inst Klin Physiologie Universitatsklinikum Ben Frkln Berlin Germany
  • H Thieme
    Inst Klin Physiologie Universitatsklinikum Ben Frkln Berlin Germany
  • A Ottlecz
    Novartis Ophthalmics AG Basle Switzerland
  • GN Lambrou
    Novartis Ophthalmics AG Basle Switzerland
  • Footnotes
    Commercial Relationships    M. Wiederholt, Novartis Ophthalmics AG F; K. Steinhausen, None; H. Thieme, None; A. Ottlecz, Novartis Ophthalmics AG E; G.N. Lambrou, Novartis Ophthalmics AG E. Grant Identification: Support: Novartis Ophthalmics AG, Basle, Switzerland
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 4085. doi:
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      M Wiederholt, K Steinhausen, H Thieme, A Ottlecz, GN Lambrou; The Effects of Unoprostone on L-type Ca2+ Channels of Human Trabecular Meshwork Cells . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4085.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract: : Purpose: The docosanoid unoprostone has been shown to reduce intraocular pressure (IOP) in patients with both ocular hypertension or primary open angle glaucoma. Trabecular meshwork (TM) in cooperation with the ciliary muscle is involved in the regulation of aqueous humour outflow and IOP. Measurements of contractility of TM revealed that unoprostone relaxes TM precontracted with endothelin (ET-1) via interference with maxi-K+ channels and Ca2+i (IOVS 42: S835, 2001). L-type Ca2+ currents of TM cells are known to influence contractility of TM (EER 70: 285-293, 2000). To further clarify the signal transduction pathways effected by unoprostone, we examined the effect of unoprostone on L-type Ca2+ currents of human trabecular meshwork (HTM) cells. Methods: Cultured HTM cells were studied using the perforated patch configuration of the patch-clamp technique. Results: Application of endothelin, ET-1 (5x10-8 M) had no influence on L-type Ca 2+ current amplitude or kinetics. In the presence and in the absence of ET-1, unoprostone reversibly inhibited L-type Ca2+ currents of HTM cells. This effect was dose-dependent. Application of unoprostone 10-6 M lead to a significant reduction to 90 1.5 % ( p < 0.01, n= 6; recovery 99.4 0.6 %) of control current, a concentration of 10-5 M reduced control current to 81 2.6 % ( p< 0.01, n= 11, recovery 97 1%), and unoprostone 10-4 M lead to a reduction to 77 4.5 % (p < 0.05, n= 4, recovery 94 4 %). After preincubation of HTM cells with the tyrosine kinase inhibitor herbimycin (10-6 M), application of unoprostone (10-5 M) had no effect on L-type Ca2+ current amplitude. After preincubation with herbimycin these cells showed a significant (p < 0.05) reduced current density (11 1.7 pA/pF, n=11) than control cells (28 4 pA/pF, n= 35) and inactivated much slower. Conclusion: Unoprostone inhibits L-type Ca2+channels of HTM cells in the presence and absence of ET-1. This effect is probably mediated by tyrosine kinases. In addition to maxi-K+ channels, L-type Ca2+ channels of HTM cells influence trabecular meshwork contractility. Activation of maxi-K+ and inhibition of L-type Ca2+ channels lead to a decline in Ca2+i and contribute to the relaxation observed in TM after application of unoprostone.

Keywords: 445 ion channels • 503 outflow: trabecular meshwork • 581 signal transduction: pharmacology/physiology 

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