advertisement
Abstract #5626 Published in IGR 2-1
Influence of muscarinic agonists and tyrosine kinase inhibitors on L-type Ca(2+)Channels in human and bovine trabecular meshwork cells
Steinhausen K; Stumpff F; Strauss O; Thieme H; Wiederholt MExperimental Eye Research 2000; 70: 285-293
Trabecular meshwork (TM), a smooth muscle-like tissue with contractile properties, is involved in the regulation of aqueous humor outflow. However, little is known about the regulation of Ca(2+) influx in trabecular meshwork cells. The authors investigated the influence of acetylcholine and tyrosine kinases on Ca(2+) conductances of bovine TM (BTM) and human TM (HTM) cells using the perforated-patch configuration of the patch-clamp technique and measurements of intracellular free Ca (2+)((Ca(2+))(i)). Depolarization of the cells in the presence of 10 mm Ba(2+)or Ca(2+) led to an activation of inward currents at potentials positive to -30 mV with characteristics typical of L-type Ca (2+) currents: when using 10 mm Ba(2+), maximal inward current and inactivation time constant (tau) increased; the L-type Ca(2+) channel blocker nifedipine (1 μm) reduced and the L-type Ca(2+) channel agonist BayK8644 (5 μm) enhanced maximal inward current. Acetylcholine (100 μm) and carbachol (1 μm) led to an increase in inward Ba (2+) current, whereas application of the tyrosine kinase inhibitors genistein (50 μm) and lavendustin A (20 μm) resulted in a decrease in inward current. The application of daidzein (10 μm), an inactive analogue of genistein had no effect. Depolarization of the cells with 135 mm K(+) or direct stimulation of L-type channels by application of BayK 8644 led to an increase in (Ca(2+))(i). Carbachol (1 μm) induced an increase in (Ca(2+))(i) which was decreased by application of the tyrosine kinase inhibitor genistein (50 μm). The authors conclude that HTM and BTM cells express voltage-dependent L-type Ca (2+) channels that influence intracellular Ca(2+) concentration and thus may modulate TM contractility. The activity of L-type Ca(2+) currents is influenced by muscarinic agonists and tyrosine kinases.
Dr. K. Steinhausen, Institüt für Klinische Physiologie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, Berlin, 12200, Germany. steinhausen@ukbf.fu-berlin.de
Classification:
4 Tissue culture of ocular cells
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
