Abstract
BackgroundThe rate-limiting step that determines the dominant time constant (τD) of mammalian rod photoresponse recovery is the deactivation of the active phosphodiesterase (PDE6). Physiologically relevant Ca2+-dependent mechanisms that would affect the PDE inactivation have not been identified. However, recently it has been shown that τD is modulated by background light in mouse rods.Methodology/Principal FindingsWe used ex vivo ERG technique to record pharmacologically isolated photoreceptor responses (fast PIII component). We show a novel static effect of calcium on mouse rod phototransduction: Ca2+ shortens the dominant time constant (τD) of saturated photoresponse recovery, i.e., when extracellular free Ca2+ is decreased from 1 mM to ∼25 nM, the τD is reversibly increased ∼1.5–2-fold.ConclusionsWe conclude that the increase in τD during low Ca2+ treatment is not due to increased [cGMP], increased [Na+] or decreased [ATP] in rod outer segment (ROS). Also it cannot be due to protein translocation mechanisms. We suggest that a Ca2+-dependent mechanism controls the life time of active PDE.
Highlights
In all eukaryotic cells a very steep gradient of Ca2+ exists across the plasma membrane
We conclude that the increase in tD during low Ca2+ treatment is not due to increased [cGMP], increased [Na+] or decreased [ATP] in rod outer segment (ROS)
We suggest that a Ca2+-dependent mechanism controls the life time of active PDE
Summary
In all eukaryotic cells a very steep gradient of Ca2+ exists across the plasma membrane. Light closes cGMP-gated channels, which reduces the influx of calcium while the calcium extrusion by the NCKX is continued, leading to a decrease in the intracellular calcium concentration. These changes in [Ca2+]i during photoresponses are used as negative feedback signals in phototransduction. In mouse rods [Ca2+]i is ,250 nM in darkness and declines to ,20– 50 nM during bright illumination [1,2] This decrease in Ca2+ accelerates both the synthesis of cGMP [3,4] and the inactivation of activated rhodopsin, R* [5,6]. Recently it has been shown that tD is modulated by background light in mouse rods
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