Clint Makino completed his PhD at Florida State University and postdoctoral studies at Stanford University School of Medicine. He is currently an Associate Professor of Physiology and Biophysics at Boston University School of Medicine. He has published more than 50 journal papers and book chapters and serves on the editorial board of Frontiers in Molecular Neuroscience.


In the first step of vision, retinal rods and cones capture light and generate an electrical response. Upon photoexcitation, the visual pigment activates a G protein coupled cascade that results in hydrolysis of the ROS-GC guanylate cyclase-generated cGMP, closure of cyclic nucleotide gated (CNG) cation channels and membrane hyperpolarization. To control the growth of the response and to speed up the recovery, there is a negative feedback loop based on free [Ca2+]. In darkness, Ca2+ enters the photoreceptor through the CNG channel. Channel closure by induced by light prevents Ca2+ entry, but continued extrusion by an exchanger causes the intracellular [Ca2+] to fall. Guanylate cyclase activating proteins (GCAPs) sense the fall and stimulate the ROS-GC catalytic activity to regenerate cGMP. As cGMP returns to the resting levels present in darkness, CNG channels re-open, Ca2+ enters and cGMP synthesis slows to its basal rate. In the presented pardigm, bicarbonate stimulates the membrane guanylate cyclase independently of Ca2+. But in the presence of GCAPs and low Ca2+, the impact of bicarbonate is greater than the sum of each factor in isolation. This synergism between bicarbonate and GCAPs at low Ca2+ has the physiological effect of boosting the maximal response amplitude, quickening photon response recovery and reducing sensitivity to flashes and to steady light.