Diffusion of lactate and its role in determining intracellular pH in the lens of the eye

Bassnett, Steven; Croghan, P. C.; Duncan, G.

doi:10.1016/s0014-4835(87)80032-5

Cited by 44 publications

(20 citation statements)

References 3 publications

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“…In contrast to our previous observations for truncated Cx49, truncated Cx46 channels did not lose their pH dependence, as shown in Fig. 4 which compares the pH depen- 4 ] + solutions that consecutively lower pH i,calc result in fast, stepwise reductions of junctional current that is completely reversible. b Hill plots for the normalized steady-state conductances for full-length rat Cx46 (filled squares) and ovine Cx49 (open circles).…”

Section: Ph Dependence Of Truncated Cx46contrasting

confidence: 99%

“…This is due to the anaerobic metabolism of glucose that most of the lens fibre cells rely on for energy production, the end product of which is lactic acid. This metabolic intermediate accumulates in the lens core rendering it acidic, while the periphery maintains normal pH levels around pH 7.2 [3,4,20]. In the lens core pH i may be as low as pH 6.5 which would almost completely abolish junctional coupling for gap junction channels consisting of full-length connexins.…”

Section: Ph Gating Of Lens Connexins and Cataractmentioning

confidence: 99%

“…This metabolism utilizes glucose as the main source of energy, converting it into lactate and consequently leading to an accumulation of lactic acid towards the lens core. This gradient in lactic acid concentration is responsible for the pH gradient within the lens [4]. In diabetes, lactate production, and thus the pH gradient, may be changed, extending the low-pH zone into the lens periphery where channels containing uncleaved connexins may then close.…”

Section: Introductionmentioning

confidence: 99%

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pH gating of lens fibre connexins

Eckert

2002

Pflugers Arch - Eur J Physiol

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Chemical gating of gap junction channels by intracellular pH may be an important mechanism for the physiological regulation of cell-cell coupling. In the ocular lens, pH gating of gap junction channels has been implicated as a possible cause of cataract in diabetics. To address this question further, I determined the pH dependence of the rat connexin (Cx)-46 and ovine Cx49 in transfected HeLa cells using the pH-clamp technique during dual whole-cell recording. pH gating for both connexins was fast and reversible. The apparent p K(a) (p K(a,app)) was 6.66 +/- 0.01 and the Hill coefficient ( n) 6.8 +/- 1.8 for Cx49, and for Cx46 6.8 +/- 0.01 and 2.2 +/- 0.15, respectively. C-terminal truncation of Cx46 by 163 aa did not abolish the pH sensitivity but shifted the p K(a,app) to 6.6 +/- 0.01. This finding is inconsistent with the ball-and-chain model proposed for Cx43. Voltage gating of Cx46 channels was also not altered by truncation or acidic pH, indicating that the two gating mechanisms are functionally and possibly structurally separate. The data also imply a significant role of pH gating for lens pathophysiology. For the normal pH range in the lens cortex (pH 6.8-7.2) most gap junction channels will be open. However, mild acidification will reduce gap junctional coupling significantly, especially for Cx50 channels. Localized closure of gap junction channels will disrupt lens transport and thus may contribute to the tissue damage observed in diabetic lenses.

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Section: Ph Dependence Of Truncated Cx46contrasting

confidence: 99%

Section: Ph Gating Of Lens Connexins and Cataractmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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pH gating of lens fibre connexins

Eckert

2002

Pflugers Arch - Eur J Physiol

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“…As the volume of the lens increases, many standing gradients will be established because of the avascularity of the tissue and the slow diffusion limited exchange of metabolites with the surrounding humors of the eye. For example, glycolysis in the bulk of the tissue results in the establishment of a lactic acid gradient (Bassnett, Croghan and Duncan, 1987) and, consequently, a gradient of intracellular pH (Bassnett et al, 1987;Mathias, Riquelme and Rae, 1991). Any metabolite, diffusing from the surface and consumed by the lens, will be at the lowest concentration in the lens core.…”

Section: Triggermentioning

confidence: 99%

Lens Organelle Degradation

Bassnett

2002

Experimental Eye Research

245

176

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“…Lactic acid generated by glycolysis diffuses from the lens only across its outer surface. Consequently, a standing gradient of lactic acid is established (Bassnett et al, 1987), resulting in values for core lens pHi that are significantly lower than those in the outer cortex (Bassnett and Duncan, 1986;Mathias et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

The effect of elevated intraocular oxygen on organelle degradation in the embryonic chicken lens

Bassnett

McNulty

2003

Journal of Experimental Biology

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SUMMARY In the vertebrate lens, nuclei and other cytoplasmic organelles are degraded in fiber cells situated in the center of the tissue. This is believed to ensure the transparency of the tissue. The mechanism that triggers this process is unknown. We hypothesized that standing gradients of oxygen generated within the tissue may serve as a spatial cue for organelle degradation. To examine this possibility, we incubated fertilized chicken eggs under hyperoxic (50% O2) or normoxic (21% O2)conditions. Hyperoxic treatment was initiated on the seventh day of embryonic development (E7), five days before organelle degradation normally commences in the lens core. Hyperoxia was maintained until E17. Under normoxic conditions,the partial pressure of oxygen (PO) within the vitreous compartment was low. Direct measurement of PO using an optode oxygen sensor indicated values of 1.3 kPa and 0.4 kPa for the mid- and anterior vitreous, respectively. Similarly, treatment with pimonidazole, a bio-reductive hypoxia marker, led to the formation of immuno-positive protein adducts within the lens, suggesting that the embryonic lens is chronically hypoxic in situ. Following hyperoxic treatment, vitreous PO significantly increased, although pimonidazole staining in the lens was not markedly affected. Confocal microscopy of slices prepared from hyperoxic lenses revealed a significant increase in the size of the lens relative to age-matched normoxic controls. By E13, an organelle-free zone(OFZ) was present in the center of normoxic and hyperoxic lenses. However, in hyperoxic lenses, the OFZ was consistently smaller, and the distance from the lens surface to the border of the OFZ significantly larger, than in normoxic controls. These observations suggest that hyperoxia delays organelle breakdown and are consistent with a model in which hypoxia in the deep cortical layers of the normal lens serves as a trigger for the organelle loss process.

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Diffusion of lactate and its role in determining intracellular pH in the lens of the eye

Cited by 44 publications

References 3 publications

pH gating of lens fibre connexins

pH gating of lens fibre connexins

Lens Organelle Degradation

The effect of elevated intraocular oxygen on organelle degradation in the embryonic chicken lens

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