Abstract

The purpose of this study is to determine the mechanisms of action involved in the ocular hypertension induced by 4-aminopyridine (4-AP), a voltage-dependent potassium (K<sup>+</sup>) channel blocker, in rabbits. Topical application of 4-AP elevated intraocular pressure (IOP). This action caused increases in the aqueous flow rate as well as aqueous levels of protein and norepinephrine. In isolated iris-ciliary body preparations, 4-AP (0.01, 0.1, 1 mmol/l) caused dose-related increases in field-stimulated norepinephrine release by 43, 222 and 243%, respectively. Taken together, the IOP-elevating effect evoked by 4-AP was associated with enhancement of aqueous norepinephrine levels and norepinephrine release from sympathetic nerves of the iris-ciliary body. These results demonstrate that the 4-AP-sensitive K<sup>+</sup> channels in sympathetic nerves and the ciliary epithelium are the potential sites of action of the 4-AP-induced ocular hypertension.

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