The retina's photoreceptor cells adjust their sensitivity to allow
photons to be transduced over a wide range of light intensities. One
mechanism thought to participate in sensitivity adjustments is
Ca
2+
regulation of guanylate cyclase (GC) by guanylate
cyclase-activating proteins (GCAPs). We evaluated the contribution of
GCAPs to sensitivity regulation in rods by disrupting their expression
in transgenic mice. The GC activity from GCAPs−/− retinas showed no
Ca
2+
dependence, indicating that Ca
2+
regulation of GCs had indeed been abolished. Flash responses from
dark-adapted GCAPs−/− rods were larger and slower than responses
from wild-type rods. In addition, the incremental flash sensitivity of
GCAPs−/− rods failed to be maintained at wild-type levels in bright
steady light. GCAP2 expressed in GCAPs−/− rods restored maximal
light-induced GC activity but did not restore normal flash response
kinetics. We conclude that GCAPs strongly regulate GC activity in mouse
rods, decreasing the flash sensitivity in darkness and increasing the
incremental flash sensitivity in bright steady light, thereby extending
the rod's operating range.