Structural features underlying retention of the SERCA pump in intracellular compartments and the sorting of the PMCA pump to the plasma membrane are not known. The biochemical properties of the two pumps suggest that their differential localization may respond to specific functional demands. The two pumps may control Ca(2+) gradients of different magnitude and dynamic properties. For instance, it has recently become clear that the Ca(2+) gradient across the endoplasmic reticulum (ER) membrane is smaller than that across the plasma membrane. Previous experiments with chimerical constructs of the SERCA and PMCA pumps had suggested a role for the amino-terminal domain in the ER retention of the SERCA pump. Experiments aimed at narrowing down the region responsible for the retention now indicate that the first 28 amino acids of the SERCA pump may play a role in membrane localization. Results also suggest that the formation of oligomers (possibly through the first 28 amino acids) might be critical to the retention mechanism.
Two types of Na+/Ca2+‐exchangers have been characterized in the literature: The first is the cardiac, skeletal muscle and brain type, which exchanges 1 Ca2+ for 3 Na+, the second, found in retinal photosensor cells, transports 1 Ca2+ and 1 K+ in exchange for 4 Na+. The present work describes the properties of chimeric constructs of the two exchanger types. Ca2+ gel overlay experiments have identified a high affinity (Kd in the 1 µm range) Ca2+‐binding domain between Glu601 and Asp733 in the main cytosolic loop of the retinal protein, just after transmembrane domain 5. Insertion of the retinal Ca2+‐binding domain in the cytosolic loop of the cardiac exchanger conferred K+‐dependence to the Ca2+ uptake activity of the chimeric constructs expressed in HeLa cells. The apparent Km of the K+ effect was about 1 mm. Experiments with C‐terminally truncated versions of the retinal insert indicated that the sequence between Leu643 and Asp733 was critical in mediating K+ sensitivity of the recombinant chimeras. Thus, the high affinity Ca2+‐binding domain in the main cytosolic loop of the retinal exchanger may regulate the activity of the retinal protein by binding Ca2+, and by conferring to it K+ sensitivity.
Can a very low intensity signal overcome a disturbance, the power density of which is much higher than the signal one, and yield some observable effects? The Johnson noise seems to be a disturbance so high as to cause a negative answer to that question, when one studies the effects on the cell level due to the external ELF fields generated by electric power lines (Adair, 1990, 1991). About this subject, we show that the masking effect due to the Johnson noise, known as “Adair’s constraint” and still present in the scientific debate, can be significantly weakened. The values provided by the Johnson noise formula, that is an approximate expression, can be affected by a significant deviation with respect to the correct ones, depending on the frequency and the kind of the cells, human or not human, that one is dealing with. We will give some examples. Eventually, we remark that the so-called Zhadin effect, although born and studied in a different context, could be viewed as an experimental test that gives an affirmative answer to the initial question, when the signal is an extremely weak electromagnetic field and the disturbance is a Johnson noise.
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