Skip to main content
Top
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology 5/2011

01-05-2011 | Basic Science

Nifedipine alters the light-rise of the electro-oculogram in man

Author: Paul A Constable

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 5/2011

Login to get access

Abstract

Background

To determine if the L-type calcium channel participates in the generation of the light-rise of the electro-oculogram (EOG) in man. The aim was to use nifedipine, a specific, L-type calcium channel inhibitor and determine the effects on the light-rise of the EOG in healthy participants.

Methods

The EOG was recorded in 14 participants before and after a 10 mg oral dose of fast-acting nifedipine. The Arden index, time to peak of the EOGs and pulse were recorded before and after ingestion of nifedipine. The test–retest variability of the EOG’s light-rise in the absence of nifedipine was performed on 11 of the participants. The mean ± SEM oral dose was 147 ± 9 μg/kg. Scotopic electroretinograms (ERGs) were recorded at four intensities (0.0067, 0.0849, 0.364 and 1.140 cd.s.m-2) in six participants before and after a 10 mg oral dose of nifedipine.

Results

The light-rise of the EOG was significantly reduced in five participants by −22.80 ± 5.6% (p = 0.021), whilst in four of the participants the light-rise increased by +15.7 ± 1.9% (p = 0.033). The results of the test–retest EOGs showed a range of −9.1 to +9.8% Arden index in the absence of nifedipine. Thus, the responses of five participants were not included in the analysis, as the change in the EOG with nifedipine was within this range. The differences in the time to peak of the light-rise were not significantly different in those that showed an increase (p = 0.33) or a decrease (p = 0.87) in the EOG after nifedipine. Pulse rate was not significantly different after nifedipine in the group that showed an increased light-rise (p = 0.77) or in those whose light-rise fell after nifedipine (p = 0.33). No significant effect was observed on the a- and b-wave amplitudes and implicit times for the scotopic components of the scotopic ERG.

Conclusions

The L-type calcium channel contributes to the light-rise of the EOG in man.
Literature
1.
go back to reference Arden GB, Barrada A, Kelsey JH (1962) A new clinical test of retinal function based upon the standing potential of the eye. Br J Ophthalmol 46:449–467PubMedCrossRef Arden GB, Barrada A, Kelsey JH (1962) A new clinical test of retinal function based upon the standing potential of the eye. Br J Ophthalmol 46:449–467PubMedCrossRef
3.
go back to reference Peterson WM, Meggyesy C, Yu K, Miller SS (1997) Extracellular ATP activates calcium signaling, ion, and fluid transport in retinal pigment epithelium. J Neurosci 17:2324–2337PubMed Peterson WM, Meggyesy C, Yu K, Miller SS (1997) Extracellular ATP activates calcium signaling, ion, and fluid transport in retinal pigment epithelium. J Neurosci 17:2324–2337PubMed
4.
go back to reference Reigada D (2005) Mitchell CH (2005) Release of ATP from retinal pigment epithelial cells involves both CFTR and vesicular transport. Am J Physiol 288:C132–C140 Reigada D (2005) Mitchell CH (2005) Release of ATP from retinal pigment epithelial cells involves both CFTR and vesicular transport. Am J Physiol 288:C132–C140
5.
go back to reference Quinn RH, Quong JN, Miller SS (2001) Adrenergic receptor activated ion transport in human fetal retinal pigment epithelium. Invest Ophthalmol Vis Sci 42:255–264PubMed Quinn RH, Quong JN, Miller SS (2001) Adrenergic receptor activated ion transport in human fetal retinal pigment epithelium. Invest Ophthalmol Vis Sci 42:255–264PubMed
6.
go back to reference Rudolf G, Vivien-Roels B, Pevet P, Kempf E, Wioland N (1992) Dopamine and melatonin interactions in the intact chicken eye. Electrooculographic and biochemical study. Brain Res 584:64–70PubMedCrossRef Rudolf G, Vivien-Roels B, Pevet P, Kempf E, Wioland N (1992) Dopamine and melatonin interactions in the intact chicken eye. Electrooculographic and biochemical study. Brain Res 584:64–70PubMedCrossRef
7.
go back to reference Weleber RG (1989) Fast and slow oscillations of the electro-oculogram in Best's macular dystrophy and retinitis pigmentosa. Arch Ophthalmol 107:530–537PubMed Weleber RG (1989) Fast and slow oscillations of the electro-oculogram in Best's macular dystrophy and retinitis pigmentosa. Arch Ophthalmol 107:530–537PubMed
8.
go back to reference Tsunenari T, Nathans J, Yau K-W (2006) Ca2+-activated Cl- current from human bestrophin-4 in excised membrane patches. J Gen Physiol 127:749–754PubMedCrossRef Tsunenari T, Nathans J, Yau K-W (2006) Ca2+-activated Cl- current from human bestrophin-4 in excised membrane patches. J Gen Physiol 127:749–754PubMedCrossRef
9.
go back to reference Qu Z, Wei RW, Mann W, Hartzell HC (2003) Two bestrophins cloned from Xenopus laevis oocytes express Ca2+-activated Cl- currents. J Biol Chem 278:49563–49572PubMedCrossRef Qu Z, Wei RW, Mann W, Hartzell HC (2003) Two bestrophins cloned from Xenopus laevis oocytes express Ca2+-activated Cl- currents. J Biol Chem 278:49563–49572PubMedCrossRef
10.
go back to reference Neussert R, Müller C, Milenkovic V, Strauss O (2010) The presence of bestrophin-1 modulates the Ca2+ recruitment from Ca2+ stores in the ER. Pflügers Archiv 460:163–175PubMedCrossRef Neussert R, Müller C, Milenkovic V, Strauss O (2010) The presence of bestrophin-1 modulates the Ca2+ recruitment from Ca2+ stores in the ER. Pflügers Archiv 460:163–175PubMedCrossRef
11.
go back to reference Rosenthal R, Bakall B, Kinnick T, Peachey N, Wimmers S, Wadelius C, Marmorstein A, Strauss O (2006) Expression of bestrophin-1, the product of the VMD2 gene, modulates voltage-dependent Ca2+ channels in retinal pigment epithelial cells. FASEB J 20:178–180PubMed Rosenthal R, Bakall B, Kinnick T, Peachey N, Wimmers S, Wadelius C, Marmorstein A, Strauss O (2006) Expression of bestrophin-1, the product of the VMD2 gene, modulates voltage-dependent Ca2+ channels in retinal pigment epithelial cells. FASEB J 20:178–180PubMed
12.
go back to reference Reichhart N, Milenkovic VM, Halsband C-A, Cordeiro S, Strauss O (2010) Effect of bestrophin-1 on L-type Ca2+ channel activity depends on the Ca2+ channel beta-subunit. Exp Eye Res 91:630–639PubMedCrossRef Reichhart N, Milenkovic VM, Halsband C-A, Cordeiro S, Strauss O (2010) Effect of bestrophin-1 on L-type Ca2+ channel activity depends on the Ca2+ channel beta-subunit. Exp Eye Res 91:630–639PubMedCrossRef
13.
go back to reference Strauss O, Buss F, Rosenthal R, Fischer D, Mergler S, Stumpff F, Thieme H (2000) Activation of neuroendocrine L-type channels (α1D subunits) in retinal pigment epithelial cells and brain neurons by pp 60c-src. Biochem Biophys Res Commun 270:806–810PubMedCrossRef Strauss O, Buss F, Rosenthal R, Fischer D, Mergler S, Stumpff F, Thieme H (2000) Activation of neuroendocrine L-type channels (α1D subunits) in retinal pigment epithelial cells and brain neurons by pp 60c-src. Biochem Biophys Res Commun 270:806–810PubMedCrossRef
14.
go back to reference Mergler S, Steinhausen K, Wiederholt M, Strauss O (1998) Altered regulation of L-type channels by protein kinase C and protein tyrosine kinases as a pathophysiologic effect in retinal degeneration. FASEB J 12:1125–1134PubMed Mergler S, Steinhausen K, Wiederholt M, Strauss O (1998) Altered regulation of L-type channels by protein kinase C and protein tyrosine kinases as a pathophysiologic effect in retinal degeneration. FASEB J 12:1125–1134PubMed
15.
go back to reference Strauss O, Mergler S, Wiederholt M (1997) Regulation of L-type calcium channels by protein tyrosine kinase and protein kinase C in cultured rat and human retinal pigment epithelial cells. FASEB J 11:859–867PubMed Strauss O, Mergler S, Wiederholt M (1997) Regulation of L-type calcium channels by protein tyrosine kinase and protein kinase C in cultured rat and human retinal pigment epithelial cells. FASEB J 11:859–867PubMed
16.
go back to reference Rosenthal R, Heimann H, Agostini H, Martin G, Hansen LL, Strauss O (2007) Ca2+ channels in retinal pigment epithelial cells regulate vascular endothelial growth factor secretion rates in health and disease. Mol Vis 13:443–456PubMed Rosenthal R, Heimann H, Agostini H, Martin G, Hansen LL, Strauss O (2007) Ca2+ channels in retinal pigment epithelial cells regulate vascular endothelial growth factor secretion rates in health and disease. Mol Vis 13:443–456PubMed
17.
go back to reference Marmorstein LY, Wu J, McLaughlin P, Yocom J, Karl MO, Neussert R, Wimmers S, Stanton JB, Gregg RG, Strauss O, Peachey N, Marmorstein AD (2006) The light peak of the electroretinogram is dependent on voltage-gated calcium channels and antagonized by bestrophin (Best-1). J Gen Physiol 127:577–589PubMedCrossRef Marmorstein LY, Wu J, McLaughlin P, Yocom J, Karl MO, Neussert R, Wimmers S, Stanton JB, Gregg RG, Strauss O, Peachey N, Marmorstein AD (2006) The light peak of the electroretinogram is dependent on voltage-gated calcium channels and antagonized by bestrophin (Best-1). J Gen Physiol 127:577–589PubMedCrossRef
18.
go back to reference Arden GB, Wolf JE (2000) The human electro-oculogram: interaction of light and alcohol. Invest Ophthalmol Vis Sci 41:2722–2729PubMed Arden GB, Wolf JE (2000) The human electro-oculogram: interaction of light and alcohol. Invest Ophthalmol Vis Sci 41:2722–2729PubMed
19.
go back to reference Malcolm B, Michael M, Vaegan EZ, Mitchell B, Michael B (2006) ISCEV Standard for Clinical Electro-oculography (EOG). Doc Ophthalmol 113:205–212CrossRef Malcolm B, Michael M, Vaegan EZ, Mitchell B, Michael B (2006) ISCEV Standard for Clinical Electro-oculography (EOG). Doc Ophthalmol 113:205–212CrossRef
20.
go back to reference Marmor M, Fulton A, Holder G, Miyake Y, Brigell M, Bach M (2009) ISCEV Standard for full-field clinical electroretinography (2008 update). Doc Ophthalmol 118:69–77PubMedCrossRef Marmor M, Fulton A, Holder G, Miyake Y, Brigell M, Bach M (2009) ISCEV Standard for full-field clinical electroretinography (2008 update). Doc Ophthalmol 118:69–77PubMedCrossRef
21.
go back to reference Constable PA, Lawrenson JG, Arden GB (2006) The electro-oculogram in cystic fibrosis. Doc Ophthalmol 113:133–143PubMedCrossRef Constable PA, Lawrenson JG, Arden GB (2006) The electro-oculogram in cystic fibrosis. Doc Ophthalmol 113:133–143PubMedCrossRef
22.
go back to reference Michelson G, Warntges S, Leidig S, Lotsch J, Geisslinger G (2006) Nimodipine plasma concentration and retinal blood flow in healthy subjects. Invest Ophthalmol Vis Sci 47:3479–3486PubMedCrossRef Michelson G, Warntges S, Leidig S, Lotsch J, Geisslinger G (2006) Nimodipine plasma concentration and retinal blood flow in healthy subjects. Invest Ophthalmol Vis Sci 47:3479–3486PubMedCrossRef
23.
go back to reference Harris A, Evans DW, Cantor LB, Martin B (1997) Hemodynamic and visual function effects of oral nifedipine in patients with normal-tension glaucoma. Am J Ophthalmol 124:296–302PubMed Harris A, Evans DW, Cantor LB, Martin B (1997) Hemodynamic and visual function effects of oral nifedipine in patients with normal-tension glaucoma. Am J Ophthalmol 124:296–302PubMed
24.
go back to reference Rashid TJ, Martin U, Clarke H, Waller DG, Renwick AG, George CF (1995) Factors affecting the absolute bioavailability of nifedipine. Br J Clin Pharmacol 40:51–58PubMed Rashid TJ, Martin U, Clarke H, Waller DG, Renwick AG, George CF (1995) Factors affecting the absolute bioavailability of nifedipine. Br J Clin Pharmacol 40:51–58PubMed
25.
go back to reference Kamide K, Yang J, Matayoshi T, Takiuchi S, Horio T, Yoshii M, Miwa Y, Yasuda H, Yoshihara F, Nakamura S, Nakahama H, Miyata T, Kawano Y (2009) Genetic polymorphisms of L-type calcium channel α1C and α1D subunit genes are associated with sensitivity to the antihypertensive effects of L-type dihydropyridine calcium-channel blockers. Circ J 73:732–740PubMedCrossRef Kamide K, Yang J, Matayoshi T, Takiuchi S, Horio T, Yoshii M, Miwa Y, Yasuda H, Yoshihara F, Nakamura S, Nakahama H, Miyata T, Kawano Y (2009) Genetic polymorphisms of L-type calcium channel α1C and α1D subunit genes are associated with sensitivity to the antihypertensive effects of L-type dihydropyridine calcium-channel blockers. Circ J 73:732–740PubMedCrossRef
26.
go back to reference Marmor M, Wu K (2005) Alcohol- and light-induced electro-oculographic responses: variability and clinical utility. Doc Ophthalmol 110:227–236PubMedCrossRef Marmor M, Wu K (2005) Alcohol- and light-induced electro-oculographic responses: variability and clinical utility. Doc Ophthalmol 110:227–236PubMedCrossRef
27.
go back to reference Tomita G, Niwa Y, Shinohara H, Hayashi N, Yamamoto T, Kitazawa Y (1999) Changes in optic nerve head blood flow and retrobular hemodynamics following calcium-channel blocker treatment of normal-tension glaucoma. Int Ophthalmol 23:3–10PubMedCrossRef Tomita G, Niwa Y, Shinohara H, Hayashi N, Yamamoto T, Kitazawa Y (1999) Changes in optic nerve head blood flow and retrobular hemodynamics following calcium-channel blocker treatment of normal-tension glaucoma. Int Ophthalmol 23:3–10PubMedCrossRef
28.
go back to reference Maminishkis A, Jalickee S, Blaug SA, Rymer J, Yerxa BR, Peterson WM, Miller SS (2002) The P2Y2 receptor agonist INS37217 stimulates RPE fluid transport in vitro and retinal reattachment in rat. Invest Ophthalmol Vis Sci 43:3555–3566PubMed Maminishkis A, Jalickee S, Blaug SA, Rymer J, Yerxa BR, Peterson WM, Miller SS (2002) The P2Y2 receptor agonist INS37217 stimulates RPE fluid transport in vitro and retinal reattachment in rat. Invest Ophthalmol Vis Sci 43:3555–3566PubMed
29.
go back to reference Karl MO, Kroeger W, Wimmers S, Milenkovic VM, Valtink M, Engelmann K, Strauss O (2008) Endogenous Gas6 and Ca2+-channel activation modulate phagocytosis by retinal pigment epithelium. Cell Signal 20:1159–1168PubMedCrossRef Karl MO, Kroeger W, Wimmers S, Milenkovic VM, Valtink M, Engelmann K, Strauss O (2008) Endogenous Gas6 and Ca2+-channel activation modulate phagocytosis by retinal pigment epithelium. Cell Signal 20:1159–1168PubMedCrossRef
Metadata
Title
Nifedipine alters the light-rise of the electro-oculogram in man
Author
Paul A Constable
Publication date
01-05-2011
Publisher
Springer-Verlag
Published in
Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 5/2011
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-010-1604-6

Other articles of this Issue 5/2011

Graefe's Archive for Clinical and Experimental Ophthalmology 5/2011 Go to the issue