Subscribe to RSS
DOI: 10.1055/s-2001-15903
Georg Thieme Verlag Stuttgart · New York
Cyclic AMP and anionic currents in porcine ciliary epithelium
cAMP-induzierte Anionenkanalaktivierung im SchweineziliarkörperPublication History
Publication Date:
31 December 2001 (online)
![](https://www.thieme-connect.de/media/klimo/200105/lookinside/thumbnails/10.1055-s-2001-15903-1.jpg)
Hintergrund Diese Pilot-Studie wurde durchgeführt, um zu testen, ob im isolierten Schweineziliarkörper die Erhöhung der intrazellulären cAMP-Konzentration eine Veränderung der Membranpermeabilität für Ionenströme bewirken kann.
Methoden Änderungen im Membranpotential, ausgelöst durch Forskolin (Adenylatzyklaseactivator; 10 μM; n=4) oder das cAMP-Analogon 8-Bromoadenosine 3′,5′-cyclic monophosphothioate (8-Br-cAMP; 30 μM; n=4) wurden mittels intrazellulärer Mikroelektroden gemessen. Der Effekt von Forskolin und 8-Br-cAMP wurde ebenfalls in An- oder Abwesenheit des Anionenkanalinhibitors Diisothiocyanato-stilbene, 2,2′-Disulfonsäure (DIDS; 1 mM; n=3) untersucht.
Resultate Forskolin und 8-Br-cAMP bewirkten beide eine signifikante (p < 0,001) Membranpotenzialdepolarisation (10,4 ± 2,0 mV und 11,7 ± 1,4 mV MW ± SEM). Die Depolarisationen induziert durch Forskolin und 8-Br-cAMP wurden durch DIDS (0,1 ± 1,0 mV und 0,7 ± 0,3 mV) gehemmt (p<0,001).
Schlussfolgerung Im isolierten Schweineziliarkörper führt die Erhöhung von cAMP zu einer Depolarisierung des Membranpotentials, ein Prozess, welcher Anionenkanäle zu involvieren scheint.
Abstract
Introduction To investigate whether in the ciliary epithelium of isolated porcine ciliary body cyclic 3′,5′ adenosine monophosphate (cAMP) activates transmembrane anionic currents.
Methods Changes in membrane potential induced either by the adenylcyclase activator forskolin (10 μM; n=4) or the stable membrane permeable cAMP analog 8-bromo-adenosine 3′,5′-cyclic monophosphothioate (8-br-cAMP; 30 μM; n=4) were measured with intracellular microelectrodes. The effect of the drugs were assessed in the absence or in the presence of the non-selective anionic channel/transporter inhibitor diisothiocyanatostilbene-2,2′ disulfonic acid (DIDS; 1 mM; n=4).
Results Significant (p < 0.001) membrane potential depolarization were induced by both forskolin (11.8 ± 0.3 mV) or 8-br-cAMP (9.3 ± 0.4 mV). In the presence of DIDS, a significant (p < 0.001) inhibition of the depolarization evoked by forskolin (0.9 ± 1.1 mV) and 8-bromo-cAMP (0.7 ± 0. 2 mV) was observed.
Conclusions In the ciliary epithelium of isolated porcine ciliary body cAMP induces membrane potential depolarization through a process that could involve anionic channels.
Schlüsselwörter:
Kammerwasserproduktion - Chloridkanäle - Elektrophysiologie - Augeninnendruck - Glaukom - transepithelialer Wassertransport
Key words
Aqueous humor formation - chloride channels - electrophysiology - intraocular pressure - glaucoma - transepithelial water transport
References
-
01 Krupin T, Civan
M M. Physiologic basis of aqueous humor formation. In: Ritch R, Sields MB, Krupin T.
The glaucomas. Mosby, St Louis; 1996: 251-280 - 02 Jacob T J, Civan M M. Role of ion channels in aqueous humor formation. Am J Physiol. 1996; 271 C703-C720
- 03 Greger R, Mall M, Bleich M, Ecke D, Warth R, Riedemann N, Kunzelmann K. Regulation of epithelial ion channels by the cystic fibrosis transmembrane conductance regulator. J Mol Med. 1996; 74 527-534
- 04 Hughes B A, Segawa Y. cAMP-activated chloride currents in amphibian retinal pigment epithelial cells. J Physiol (Lond). 1993; 466 749-766
- 05 Fleischhauer J C, Bény J L, Flammer J, Haefliger I O. NO/cGMP Pathway Activation and Membrane Potential Depolarization in Pig Ciliary Epithelium. IOVS. 2000; 41 1759-1763
- 06 Fuller C M, Benos D J. CFTR!. Am J Physiol. 1992; 263 C267-C286
- 07 Civan M M, Coca-Prados M, Peterson-Yantorno K. Pathways signaling the regulatory volume decrease of cultured nonpigmented ciliary epithelial cells. Invest Ophthalmol Vis Sci. 1994; 35 2876-2886
- 08 Chen S, Inoue R, Inomata H, Ito Y. Role of cyclic AMP-induced Cl conductance in aqueous humour formation by the dog ciliary epithelium. Br J Pharmacol. 1994; 112 1137-1145
- 09 Chen S, Sears M. A low conductance chloride channel in the basolateral membranes of the non-pigmented ciliary epithelium of the rabbit eye. Curr Eye Res. 1997; 16 710-718
- 10 Sano N, Shichi H. Bimodal regulation of adenylate cyclase by prostaglandin E2 receptors in porcine ciliary epithelium. Prostaglandins Leukot Essent Fatty Acids. 1993; 49 765-769
- 11 Samuelsson-Almen M, Nilsson S F. Pituitary adenylate cyclase-activating polypeptide- and VIP-induced activation of adenylate cyclase in the porcine non-pigmented ciliary epithelium: effects of antagonists. J Ocul Pharmacol Ther. 1999; 15 389-400