The mechanisms of calcium homeostasis and signalling in the lens

Abstract

a b s t r a c tExcessive Ca 2þ can be detrimental to cells and raised levels of Ca 2þ in human lenses with cortical cataract have been found to play a major role in the opacification process. Ca 2þ homeostasis is therefore, recognised as having fundamental importance in lens pathophysiology. Furthermore, Ca 2þ plays a central role as a second messenger in cell signalling and mechanisms have evolved which give cells exquisite control over intracellular Ca 2þ ([Ca 2þ ] i ) via an array of specialised regulatory and signalling proteins. In this review we discuss these mechanisms as they apply to the lens. Ca 2þ levels in human aqueous humour are approximately 1 mM and there is a large, 10,000 fold, inwardly directed gradient across the plasma membrane. In the face of such a large gradient highly efficient mechanisms are needed to maintain low [Ca 2þ ] i . The Na þ /Ca 2þ exchanger (NCX) and plasma membrane Ca 2þ -ATPase (PMCA) actively remove Ca 2þ from the cells, whereas the sarco(endo)plasmic reticulum Ca 2þ -ATPase (SERCA) sequesters Ca 2þ in the endoplasmic reticulum (ER) Ca 2þ store. In lens epithelial cells the dominant role is played by the ATPases, whilst in the fibre cells NCX activity appears to be more important. Usually, [Ca 2þ ] i can be increased in a number of ways. Ca 2þ influx through the plasma membrane, for example, is mediated by an array of channels with evidence in the lens for the presence of voltage-operated Ca 2þ channels (VOCCs), receptor-operated Ca 2þ channels (ROCCs) and channels mediating store-operated Ca 2þ entry (SOCE). Ca 2þ signalling is initiated via activation of G-protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTK) of which the lens expresses a surprisingly diverse array responding to various neurotransmitters, hormones, growth factors, autocoids and proteases. Downstream of plasma membrane receptors are IP 3 -gated channels (IP 3 Rs) and ryanodine receptors (RYRs) located in the ER, which when activated cause a rapid increase in [Ca 2þ ] i and these have also been identified in the lens. Through an appreciation of the diversity and complexity of the mechanisms involved in Ca 2þ homeostasis in normal lens cells we move closer to an understanding of the mechanisms which mediate pathological Ca 2þ overload as occurs in the process of cataract formation.

Calcium-dependent protein folding in amyotrophic lateral sclerosis

“…It restores the cytosolic Ca 2+ concentration to its low resting level (100 nM) and maintains a high (500 M) luminal ER Ca 2+ concentration [16]. Ultimately, the sodium/Ca 2+ -exchanger and plasma membrane Ca 2+ ATPase remove Ca 2+ from the cell [17] ( Fig. 1).…”

The Effect of Gentian Violet on Human Anterior Lens Epithelial Cells

“…Calcium ions are of vital importance to many physiological processes and their concentrations are maintained within specific limits to ensure adequate homeostasis. 9 There is a wide consensus that the dis-regulation of the free intracellular calcium concentration ([Ca 2+ ] i ) and its pathological increase eventually lead to mechanisms causing some form of cell death. 10 The exact form/type of cell death is usually determined by the cell's physiological parameters accompanying the triggering events.…”

Scientific evidence contradicts findings and assumptions of Canadian Safety Panel 6: microwaves act through voltage-gated calcium channel activation to induce biological impacts at non-thermal levels, supporting a paradigm shift for microwave/lower frequency electromagnetic field action

“…Walsh and Patterson (72) demonstrated that elevated [Ca2+]i in the lens of the frog eye has a central role in cataract formation and that calcium channel blockers, which of course block VGCC activation, can block cataract formation. In a recent review, it was shown that excessive [Ca2+]i in the lens of the human and mammalian eye plays a major role in the opacification process producing cataracts and that VGCCs can have a substantial role in this process (73). While these studies do not directly relate to microwave exposures, they clearly show that excessive [Ca2+]i in the lens of the eye has essential roles in cataract formation and that excessive VGCC activity causes cataract formation in experimental animals.…”