Whole-cell potassium current in rabbit corneal epithelium activated by fenamates

Rae, James L.; Farrugia, Gianrico

doi:10.1007/bf00232057

Cited by 35 publications

(13 citation statements)

References 30 publications

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“…In rabbit and human corneal epithelial cells, there are voltage-gated K + (Kv) channels in the apical membrane of the superficial layers and a large conductance K + channel is also found in the basal cell layers (Rae, 1985;Rae et al, 1990;Rae and Farrugia, 1992). These channels are stimulated by fenamate, cGMP, carbachol, cell swelling, membrane stretch, CO and acidification Rae, 1992,1993;Rae and Farrugia, 1992;Rich et al, 1994Rich et al, ,1997Watanabe et al, 1997). Their activities are inhibited by barium, quinidine, diltiazem and prozac Rae et al, 1995).…”

Section: Expression Of Kv Channels In Corneal Epithelial Cellsmentioning

confidence: 99%

Stress-induced corneal epithelial apoptosis mediated by K+ channel activation

2006

Progress in Retinal and Eye Research

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One of the functional roles of the corneal epithelial layer is to protect the cornea, lens and other underlying ocular structures from damages caused by environmental insults. It is important for corneal epithelial cells to maintain this function by undergoing continuous renewal through a dynamic process of wound healing. Previous studies in corneal epithelial cells have provided substantial evidence showing that environmental insults, such as ultraviolet (UV) irradiation and other biohazards, can induce stress-related cellular responses resulting in apoptosis and thus interrupt the dynamic process of wound healing. We found that UV irradiation-induced apoptotic effects in corneal epithelial cells are started by the hyperactivation of K + channels in the cell membrane resulting in a fast loss of intracellular K + ions. Recent studies provide further evidence indicating that these complex responses in corneal epithelial cells are resulted from the activation of stressrelated signaling pathways mediated by K + channel activity. The effect of UV irradiation on corneal epithelial cell fate shares common signaling mechanisms involving the activation of intracellular responses that are often activated by the stimulation of various cytokines. One piece of evidence for making this distinction is that at early times UV irradiation activates a Kv3.4 channel in corneal epithelial cells to elicit activation of c-Jun N-terminal kinase cascades and p53 activation leading to cell cycle arrest and apoptosis. The hypothetic model is that UV-induced potassium channel hyperactivity as an early event initiates fast cell shrinkages due to the loss of intracellular potassium, resulting in the activation of scaffolding protein kinases and cytoskeleton reorganizations. This review article presents important control mechanisms that determine Kv channel activity-mediated cellular responses in corneal epithelial cells, involving activation of stress-induced signaling pathways, arrests of cell cycle progression and/or induction of apoptosis.

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Section: Expression Of Kv Channels In Corneal Epithelial Cellsmentioning

confidence: 99%

Stress-induced corneal epithelial apoptosis mediated by K+ channel activation

2006

Progress in Retinal and Eye Research

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“…A mechano-gated K + channel, namely the large conductance K + channel is responsible for the major, background K + conductance in the corneal epithelium, which is characteristically stimulated by fenamates and inhibited by diltiazem [7]. We recently discovered that this K + current in the bovine corneal epithelium is also enhanced by certain unsaturated fatty acids, including arachidonic acid [8].…”

Section: Introductionmentioning

confidence: 99%

Fenamates and diltiazem modulate lipid-sensitive mechano-gated 2P domain K+ channels

Takahira

Sakurai

Sakurada

et al. 2005

Pflugers Arch - Eur J Physiol

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A swelling-activated, background K(+) current in the corneal epithelium is characteristically activated by fenamates and inhibited by diltiazem. Fatty acids also stimulate this current, indicating that its origin is a lipid-sensitive mechano-gated 2P domain K(+) channel. In the present study, modulation of TREK-1, TREK-2, and TRAAK channels by fenamates and diltiazem was examined. TREK-1, TREK-2, and TRAAK currents transiently expressed in COS-7 cells were recorded by the perforated-patch configuration. As previously reported, arachidonic acid (20 microM) stimulated all of these channels, and a volatile anesthetic, halothane (1 mM) augmented TREK-1 and TREK-2 but not TRAAK. Flufenamic acid (FA, 100 microM), niflumic acid (NA, 100 microM), and mefenamic acid (MA, 100 microM) markedly stimulated TREK-1, TREK-2, and TRAAK. The potency sequence for the activation of TREK-1 and TREK-2 was FA > NA = MA, and the potency sequence for the activation of TRAAK was FA = NA > MA. Diltiazem (1 mM) inhibited TREK-1 and TREK-2, but not TRAAK. In conclusion, fenamates are openers of the lipid-sensitive mechano-gated 2P domain K(+) channels, and diltiazem may be a specific blocker for TREK. These novel findings could help to further understand channel functions of the mechano-gated 2P domain K(+) channels.

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“…1(A)] (Rae et al, 1990;Rae and Farrugia, 1992). There was a statistically signi®cant difference in the current density among different sized corneal epithelial cells, i.e.…”

Section: Resultsmentioning

confidence: 95%