Stimulation of maxi-K channels in trabecular meshwork by tyrosine kinase inhibitors
作者： Friederike Stumpff , Marianne Boxberger , Michael Wiederholt , Olaf Strauss , Yang Que
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摘要: Purpose Muscarinic agonists contract and tyrosine kinase inhibitors relax precontracted trabecular meshwork, a smooth muscle-like tissue involved in the regulation of aqueous humor outflow. The effect on membrane currents cells stimulated by acetylcholine was examined. Methods Cells from bovine meshwork were studied using both perforated patch-clamp technique with nystatin single-channel technique. Results Application inhibitor genistein (5 x 10(-5) M) resulted reversible increase outward current to 578%+/-154% (n = 16) initial level. dose dependent. Reversal potential hyperpolarized 15+/-3 mV 9). Tyrphostin 51, synthetic kinases, had same (433%+/-46%; n 7). Daidzein, nonactive structural analogue genistein, no 4). stimulation blocked substitution tetraethylammonium (TEA+) for potassium, whereas potassium channel blockers glibenclamide (K-ATP) apamin (low-conductance calcium-activated channel) effect. Blockage high-conductance (maxi-K) charybdotoxin or iberiotoxin (10(7) suppressed 86%+/-18% 4) response. Depleting calcium did not have an genistein. In excised inside-out configuration, open probability increased 417%+/-39% 3) after exposure Conclusions activate maxi-K (K(Ca)) channels. Hyperpolarization caused efflux could lead relaxation inhibitors.
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