Articles

Modulation of intraocular pressure by ATP sensitive potassium channel openers

Author(s):

Uttio Roy Chowdhury

Peter I. Dosa

Michael P. Fautsch


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Abstract:

ATP sensitive potassium (KATP) channels are obligatory hetero-octamers that contain four sulphonylurea receptors (SUR) and four potassium inward rectifier (Kir) subunits. While regulated by intracellular ATP/ADP concentrations, different combinations of SUR and Kir subunits impart tissue specificity and unique functionalities, including cell relaxation and protection. In recent years, pharmacologic openers of KATP channels such as diazoxide and cromakalim have been shown to significantly lower intraocular pressure in human and animal model systems through activation of the Erk1/2 signaling pathway. Development and characterization of a water-soluble cromakalim prodrug shows this novel KATP channel opener retains the ocular hypotensive properties of its parent compound, and exhibits an excellent tolerance and safety profile in preclinical animal models. This review summarizes the structural and functional characteristics of KATP channels, their pharmacologic openers and closers, and the evidence supporting their ocular hypotensive properties.

Glaucoma Research 2018-2020, pp. 205-223 #15
Edited by: John R. Samples and Paul A. Knepper
© Kugler Publications, Amsterdam, The Netherlands


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