Differential P1-purinergic modulation of human Schlemm's canal inner-wall cells

• Published in: American Journal of Physiology: Cell Physiology Vol. 288; no. 4; pp. C784 - C794
• Main Authors: Karl, Mike O, Fleischhauer, Johannes C, Stamer, W. Daniel, Peterson-Yantorno, Kim, Mitchell, Claire H, Stone, R. A, Civan, M. M
• Format: Journal Article
• Language: English
• Published: United States 01.04.2005
• Subjects: Anterior Eye Segment - cytology; Anterior Eye Segment - metabolism; Aqueous Humor - physiology; Calcium - metabolism; Cell Culture Techniques - methods; Cells, Cultured; Humans; Intracellular Fluid - drug effects; Intracellular Fluid - metabolism; Intraocular Pressure - drug effects; Intraocular Pressure - physiology; Membrane Potentials - drug effects; Patch-Clamp Techniques; Purinergic P1 Receptor Agonists; Purinergic P1 Receptor Antagonists; Receptors, Purinergic P1 - drug effects; Receptors, Purinergic P1 - physiology
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00333.2004

1 Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia; 2 Department of Ophthalmology, University of Arizona, Tucson, Arizona; and 3 Departments of Ophthalmology and 4 Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania Submitted 9 July 2004 ; accepted in final form 5 December 2004 Intraocular pressure is directly dependent on aqueous humor flow into, and resistance to flow out of, the eye. Adenosine has complex effects on intraocular pressure. Stimulation of A 1 and A 2A adenosine receptors changes intraocular pressure oppositely, likely through opposing actions on the outflow of aqueous humor. While the cellular sites regulating outflow resistance are unknown, the cells lining the inner wall of Schlemm's canal (SC) are a likely regulatory site. We applied selective adenosine receptor agonists to SC cells in vitro to compare the responses to A 1 and A 2A stimulation. Parallel studies were conducted with human inner-wall SC cells isolated by a novel enzyme-assisted technique and with cannula-derived mixed inner- and outer-wall SC cells. A 1 agonists increased whole cell currents of both inner-wall and cannula-derived SC cells. An A 2A agonist reduced currents most consistently in specifically inner-wall SC cells. Those currents were also increased by A 2B , but not consistently affected by A 3 , stimulation. A 1 , A 2A , and A 3 agonists all increased SC-cell intracellular Ca 2+ . The electrophysiological results are consistent with the possibility that inner-wall SC cells may mediate the previously reported modulatory effects of adenosine on outflow resistance. The results are also consistent with the presence of functional A 2B , as well as A 1 , A 2A , and A 3 adenosine receptors in SC cells. intraocular pressure; aqueous humor outflow; ion transport; adenosine agonists Address for reprint requests and other correspondence: M. M. Civan, Dept. of Physiology, A303 Richards Bldg., Univ. of Pennsylvania, Philadelphia, PA 19104-6085 (E-mail: civan{at}mail.med.upenn.edu )