INTRODUCTION
Ca2+ as an intracellular second messenger is indispensable for the physiology of organisms and the molecular regulation of cells. The cytosolic free Ca2+ concentration is a crucial signal for a variety of neuronal processes including neurotransmitter release, control of membrane excitability, synaptic plasticity, and cognition. Ca2+ homeostasis in neurons is accurate controlled by several types of Ca2+ channels or the activity of Ca2+ transporters with either locate on the plasma membrane or inside the cell on endoplasmic reticulum (ER) / sarcoplasmic reticulum (SR) (1,2). Disturbance of calcium homeostasis is implicated in the normal process of aging and the brain pathology prevalent in many neurodegeneration diseases and neurotoxicity. …show more content…
What is more, emerging evidences suggest that, by controlling levels of cytoplasmic free Ca2+ locally in growth cones and synaptic compartments, RyRs regulate functional and structural changes in nerve cell circuits in both the developing and adult nervous systems (5), and alterations in Ca2+ homeostasis by RyRs contribute to neuronal apoptosis and excitotoxicity, which are being linked to the pathogenesis of several different neurodegenerative disorders (2,6,7).
Lead ion (Pb2+) is a neurotoxin that continues to be considered a major global environmental health hazard. However, the mechanism underlying Pb2+ is not fully understood. so far, the effects of Pb2+ on cytosolic free Ca2+ concentration and calcium-regulated events have always been suggested as the major mechanisms involved in Pb2+ toxicity …show more content…
In addition, Pb2+ appears to resemble Ca2+ sufficiently closely to disrupt calcium homeostasis and affect calcium signal conduct，which then results in neurotoxicity and other health damage (12-14). What is amazing is that the neurodevelopmental disorders or degenerative diseases, which have been shown to be caused by disorder in RyRs (6,7), have also been identified to be caused by exposing to lead (15,16). Further, previous research results in our laboratory indicate that lead exposure affects RyRs both cultured cells (17) and rats level (data is yet unpublished). However, whether there are interactional potential between their molecules is under elucidated and still needed for further
Ca2+ as an intracellular second messenger is indispensable for the physiology of organisms and the molecular regulation of cells. The cytosolic free Ca2+ concentration is a crucial signal for a variety of neuronal processes including neurotransmitter release, control of membrane excitability, synaptic plasticity, and cognition. Ca2+ homeostasis in neurons is accurate controlled by several types of Ca2+ channels or the activity of Ca2+ transporters with either locate on the plasma membrane or inside the cell on endoplasmic reticulum (ER) / sarcoplasmic reticulum (SR) (1,2). Disturbance of calcium homeostasis is implicated in the normal process of aging and the brain pathology prevalent in many neurodegeneration diseases and neurotoxicity. …show more content…
What is more, emerging evidences suggest that, by controlling levels of cytoplasmic free Ca2+ locally in growth cones and synaptic compartments, RyRs regulate functional and structural changes in nerve cell circuits in both the developing and adult nervous systems (5), and alterations in Ca2+ homeostasis by RyRs contribute to neuronal apoptosis and excitotoxicity, which are being linked to the pathogenesis of several different neurodegenerative disorders (2,6,7).
Lead ion (Pb2+) is a neurotoxin that continues to be considered a major global environmental health hazard. However, the mechanism underlying Pb2+ is not fully understood. so far, the effects of Pb2+ on cytosolic free Ca2+ concentration and calcium-regulated events have always been suggested as the major mechanisms involved in Pb2+ toxicity …show more content…
In addition, Pb2+ appears to resemble Ca2+ sufficiently closely to disrupt calcium homeostasis and affect calcium signal conduct，which then results in neurotoxicity and other health damage (12-14). What is amazing is that the neurodevelopmental disorders or degenerative diseases, which have been shown to be caused by disorder in RyRs (6,7), have also been identified to be caused by exposing to lead (15,16). Further, previous research results in our laboratory indicate that lead exposure affects RyRs both cultured cells (17) and rats level (data is yet unpublished). However, whether there are interactional potential between their molecules is under elucidated and still needed for further