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. Ca(2+) influx via these channels is required for light adaptation, but although several molecular targets of Ca(2+)-dependent feedback have been identified, their contribution to adaptation is unclear. By manipulating cytosolic Ca(2+) via the Na(+)/Ca(2+) exchange equilibrium, we found that Ca(2+) inhibited the light-induced current (LIC) over a range corresponding to steady-state light-adapted Ca(2+) levels (0.1-10 microM Ca(2+)) and accurately mimicked light adaptation. However, PLC activity monitored with genetically targeted PIP(2)-sensitive ion channels (Kir2.1) was first inhibited by much higher (>/= approximately 50 microM) Ca(2+) levels, which occur only transiently in vivo. Ca(2+)-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 Ca(2+)-dependent inhibition of TRP channels. This is interpreted as a strategy to prevent inhibition of PLC by global steady-state light-adapted Ca(2+) levels, whereas rapid inhibition of PLC by local Ca(2+) transients is required to terminate the response and ensures that PIP(2) reserves are not depleted during stimulation.
Gu
Yuchun
Y
Department of Anatomy, Cambridge University, Downing Street, Cambridge CB2 3DY, United Kingdom. rch14@hermes.cam.ac.uk
Oberwinkler
Johannes
J
Postma
Marten
M
Hardie
Roger C
RC
D000221:Adaptation, Ocular / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000378:metabolism; D004594:Electrophysiology; D009154:Mutation / Q000235:genetics; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D017956:Photoreceptor Cells, Invertebrate / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D050051:Transient Receptor Potential Channels; D010738:Type C Phospholipases / Q000378:metabolism; D014785:Vision, Ocular / Q000502:physiology*
D015220:Calcium Channels; D029721:Drosophila Proteins; C489461:Kir2.1 channel; D019269:Phosphatidylinositol 4,5-Diphosphate; D024661:Potassium Channels, Inwardly Rectifying; D050051:Transient Receptor Potential Channels; C063169:trp protein, Drosophila; D012964:Sodium; D011493:Protein Kinase C; D010738:Type C Phospholipases; D002118:Calcium