Mechanisms of light adaptation in Drosophila photoreceptors

Phototransduction in Drosophila is mediated by a phospholipase C (PLC) cascade culminating in activation of transient receptor potential (TRP) channels [1, 2]. Ca2+ influx via these channels is required for light adaptation, but although several molecular targets of Ca2+-dependent feedback have been identified [3], their contribution to adaptation is unclear. By manipulating cytosolic Ca2+ via the Na+/Ca2+ exchange equilibrium, we found that Ca2+ inhibited the light-induced current (LIC) over a range corresponding to steady-state light-adapted Ca2+ levels (0.1-10 mu M Ca2+) and accurately mimicked light adaptation. However, PLC activity monitored with genetically targeted PIP2-sensitive ion channels (Kir2.1) was first inhibited by much higher (>= similar to 50 mu M) Ca2+ levels, which occur only transiently in vivo. Ca2+-dependent inhibition of PLC, but not the LIC, was impaired in mutants (inaC) of protein kinase C (PKC). The results indicate that light adaptation is primarily mediated downstream of PLC and independently of PKC by Ca2+-dependent inhibition of TRP channels. This is interpreted as a strategy to prevent inhibition of PLC by global steady-state light-adapted Ca2+ levels, whereas rapid inhibition of PLC by local Ca2+ transients is required to terminate the response and ensures that PIP2 reserves are not depleted during stimulation.