Synergistic modulation of the membrane guanylate cyclases in reti | 48802

Journal of Neuroscience and Neuropharmacology

Synergistic modulation of the membrane guanylate cyclases in retinal rods and cones by bicarbonate and calcium

4th Global Experts Meeting on Neuropharmacology

September 14-16, 2016 San Antonio, USA

Clint L Makino

Boston University, USA

Scientific Tracks Abstracts: Neurochem Neuropharm

Abstract :

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 reopen, Ca2+ enters and cGMP synthesis slows to its basal rate. In the presented paradigm, 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.

Biography :

Clint L Makino has completed his PhD from Florida State University and Post-doctoral studies from 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, book chapters and serves as the Editorial Board Member of Frontiers in Molecular Neuroscience.