ATP-sensitive potassium (K ATP) channel activation decreases intraocular pressure in the anterior chamber of the eye

Uttio Roy Chowdhury, Cindy K. Bahler, Cheryl R. Hann, Minhwang Chang, Zachary T. Resch, Michael F Romero, Michael P Fautsch

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Purpose. ATP-sensitive potassium channel (K ATP) openers target key cellular events, many of which have been implicated in glaucoma. The authors sought to determine whether K ATP channel openers influence outflow facility in human anterior segment culture and intraocular pressure (IOP) in vivo. Methods. Anterior segments from human eyes were placed in perfusion organ culture and treated with the K ATP channel openers diazoxide, nicorandil, and P1075 or the K ATP channel closer glyburide (glibenclamide). The presence, functionality, and specificity of K ATP channels were determined by RT-PCR, immunohistochemistry, and inside-out patch clamp in human trabecular meshwork (TM) tissue or primary cultures of normal human trabecular meshwork (NTM) cells. The effect of diazoxide on IOP in anesthetized Brown Norway rats was measured with a rebound tonometer. Results. K ATP channel openers increased outflow facility in human anterior segments (0.14 ± 0.02 to 0.26 ± 0.09 μL/min/mm Hg; P < 0.001) compared with fellow control eyes (0.22 ± 0.11 to 0.21 ± 0.11 μL/min/mm Hg; P > 0.5). The effect was reversible, with outflow facility returning to baseline after drug removal. The addition of glyburide inhibited diazoxide from increasing outflow facility. Electrophysiology confirmed the presence and specificity of functional K ATP channels. K ATP channel subunits K ir6.1, K ir6.2, SUR2A, and SUR2B were expressed in TM and NTM cells. In vivo, diazoxide significantly lowered IOP in Brown Norway rats. Conclusions. Functional K ATP channels are present in the trabecular meshwork. When activated by K ATP channel openers, these channels increase outflow facility through the trabecular outflow pathway in human anterior segment organ culture and decrease IOP in Brown Norway rat eyes.

Original languageEnglish (US)
Pages (from-to)6435-6442
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume52
Issue number9
DOIs
StatePublished - Aug 2011

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KATP Channels
Anterior Chamber
Intraocular Pressure
Adenosine Triphosphate
Trabecular Meshwork
Diazoxide
Glyburide
Organ Culture Techniques
Nicorandil
Anterior Eye Segment
Electrophysiology
Glaucoma
Perfusion
Immunohistochemistry

ASJC Scopus subject areas

  • Medicine(all)
  • Ophthalmology
  • Cellular and Molecular Neuroscience
  • Sensory Systems

Cite this

ATP-sensitive potassium (K ATP) channel activation decreases intraocular pressure in the anterior chamber of the eye. / Roy Chowdhury, Uttio; Bahler, Cindy K.; Hann, Cheryl R.; Chang, Minhwang; Resch, Zachary T.; Romero, Michael F; Fautsch, Michael P.

In: Investigative Ophthalmology and Visual Science, Vol. 52, No. 9, 08.2011, p. 6435-6442.

Research output: Contribution to journalArticle

Roy Chowdhury, Uttio ; Bahler, Cindy K. ; Hann, Cheryl R. ; Chang, Minhwang ; Resch, Zachary T. ; Romero, Michael F ; Fautsch, Michael P. / ATP-sensitive potassium (K ATP) channel activation decreases intraocular pressure in the anterior chamber of the eye. In: Investigative Ophthalmology and Visual Science. 2011 ; Vol. 52, No. 9. pp. 6435-6442.
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abstract = "Purpose. ATP-sensitive potassium channel (K ATP) openers target key cellular events, many of which have been implicated in glaucoma. The authors sought to determine whether K ATP channel openers influence outflow facility in human anterior segment culture and intraocular pressure (IOP) in vivo. Methods. Anterior segments from human eyes were placed in perfusion organ culture and treated with the K ATP channel openers diazoxide, nicorandil, and P1075 or the K ATP channel closer glyburide (glibenclamide). The presence, functionality, and specificity of K ATP channels were determined by RT-PCR, immunohistochemistry, and inside-out patch clamp in human trabecular meshwork (TM) tissue or primary cultures of normal human trabecular meshwork (NTM) cells. The effect of diazoxide on IOP in anesthetized Brown Norway rats was measured with a rebound tonometer. Results. K ATP channel openers increased outflow facility in human anterior segments (0.14 ± 0.02 to 0.26 ± 0.09 μL/min/mm Hg; P < 0.001) compared with fellow control eyes (0.22 ± 0.11 to 0.21 ± 0.11 μL/min/mm Hg; P > 0.5). The effect was reversible, with outflow facility returning to baseline after drug removal. The addition of glyburide inhibited diazoxide from increasing outflow facility. Electrophysiology confirmed the presence and specificity of functional K ATP channels. K ATP channel subunits K ir6.1, K ir6.2, SUR2A, and SUR2B were expressed in TM and NTM cells. In vivo, diazoxide significantly lowered IOP in Brown Norway rats. Conclusions. Functional K ATP channels are present in the trabecular meshwork. When activated by K ATP channel openers, these channels increase outflow facility through the trabecular outflow pathway in human anterior segment organ culture and decrease IOP in Brown Norway rat eyes.",
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T1 - ATP-sensitive potassium (K ATP) channel activation decreases intraocular pressure in the anterior chamber of the eye

AU - Roy Chowdhury, Uttio

AU - Bahler, Cindy K.

AU - Hann, Cheryl R.

AU - Chang, Minhwang

AU - Resch, Zachary T.

AU - Romero, Michael F

AU - Fautsch, Michael P

PY - 2011/8

Y1 - 2011/8

N2 - Purpose. ATP-sensitive potassium channel (K ATP) openers target key cellular events, many of which have been implicated in glaucoma. The authors sought to determine whether K ATP channel openers influence outflow facility in human anterior segment culture and intraocular pressure (IOP) in vivo. Methods. Anterior segments from human eyes were placed in perfusion organ culture and treated with the K ATP channel openers diazoxide, nicorandil, and P1075 or the K ATP channel closer glyburide (glibenclamide). The presence, functionality, and specificity of K ATP channels were determined by RT-PCR, immunohistochemistry, and inside-out patch clamp in human trabecular meshwork (TM) tissue or primary cultures of normal human trabecular meshwork (NTM) cells. The effect of diazoxide on IOP in anesthetized Brown Norway rats was measured with a rebound tonometer. Results. K ATP channel openers increased outflow facility in human anterior segments (0.14 ± 0.02 to 0.26 ± 0.09 μL/min/mm Hg; P < 0.001) compared with fellow control eyes (0.22 ± 0.11 to 0.21 ± 0.11 μL/min/mm Hg; P > 0.5). The effect was reversible, with outflow facility returning to baseline after drug removal. The addition of glyburide inhibited diazoxide from increasing outflow facility. Electrophysiology confirmed the presence and specificity of functional K ATP channels. K ATP channel subunits K ir6.1, K ir6.2, SUR2A, and SUR2B were expressed in TM and NTM cells. In vivo, diazoxide significantly lowered IOP in Brown Norway rats. Conclusions. Functional K ATP channels are present in the trabecular meshwork. When activated by K ATP channel openers, these channels increase outflow facility through the trabecular outflow pathway in human anterior segment organ culture and decrease IOP in Brown Norway rat eyes.

AB - Purpose. ATP-sensitive potassium channel (K ATP) openers target key cellular events, many of which have been implicated in glaucoma. The authors sought to determine whether K ATP channel openers influence outflow facility in human anterior segment culture and intraocular pressure (IOP) in vivo. Methods. Anterior segments from human eyes were placed in perfusion organ culture and treated with the K ATP channel openers diazoxide, nicorandil, and P1075 or the K ATP channel closer glyburide (glibenclamide). The presence, functionality, and specificity of K ATP channels were determined by RT-PCR, immunohistochemistry, and inside-out patch clamp in human trabecular meshwork (TM) tissue or primary cultures of normal human trabecular meshwork (NTM) cells. The effect of diazoxide on IOP in anesthetized Brown Norway rats was measured with a rebound tonometer. Results. K ATP channel openers increased outflow facility in human anterior segments (0.14 ± 0.02 to 0.26 ± 0.09 μL/min/mm Hg; P < 0.001) compared with fellow control eyes (0.22 ± 0.11 to 0.21 ± 0.11 μL/min/mm Hg; P > 0.5). The effect was reversible, with outflow facility returning to baseline after drug removal. The addition of glyburide inhibited diazoxide from increasing outflow facility. Electrophysiology confirmed the presence and specificity of functional K ATP channels. K ATP channel subunits K ir6.1, K ir6.2, SUR2A, and SUR2B were expressed in TM and NTM cells. In vivo, diazoxide significantly lowered IOP in Brown Norway rats. Conclusions. Functional K ATP channels are present in the trabecular meshwork. When activated by K ATP channel openers, these channels increase outflow facility through the trabecular outflow pathway in human anterior segment organ culture and decrease IOP in Brown Norway rat eyes.

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