PT  - JOURNAL ARTICLE
AU  - Ward M. Peterson
AU  - Chris Meggyesy
AU  - Kefu Yu
AU  - Sheldon S. Miller
TI  - Extracellular ATP Activates Calcium Signaling, Ion, and Fluid Transport in Retinal Pigment Epithelium
AID  - 10.1523/JNEUROSCI.17-07-02324.1997
DP  - 1997 Apr 01
TA  - The Journal of Neuroscience
PG  - 2324--2337
VI  - 17
IP  - 7
4099  - http://www.jneurosci.org/content/17/7/2324.short
4100  - http://www.jneurosci.org/content/17/7/2324.full
SO  - J. Neurosci.1997 Apr 01; 17
AB  - The presence of receptors for ATP has not been established in any native preparation of retinal neurons or glia. In the present study, we used conventional electrophysiological and [Ca2+]in fluorescence imaging techniques to investigate the effects of ATP added to Ringer’s solution perfusing the retinal-facing (apical) membrane of freshly isolated monolayers of bovine retinal pigment epithelium (RPE). ATP (or UTP) produced large, biphasic voltage and resistance changes with aKd of ∼5 μm for ATP and ∼1 μm for UTP. Electrical and pharmacological evidence indicates that the first and second phases of the response are attributable to an increase in basolateral membrane Cl conductance and a decrease in apical membrane K conductance, respectively. The ATP-induced responses were not affected by adenosine, but were reduced by the P2-purinoceptor blocker suramin. ATP also produced a large, transient increase in [Ca2+]in that was blocked by cyclopiazonic acid, an inhibitor of endoplasmic reticulum Ca2+-ATPases. The calcium buffer BAPTA attenuated the voltage effects of ATP. We also found that apical DIDS significantly inhibited the ATP-evoked [Ca2+]in and electrical responses, suggesting that DIDS blocked the purinoceptor. Measurements of fluid movement across the RPE using the capacitance probe technique demonstrated a significant increase in fluid absorption by apical UTP. These data indicate the presence of metabotropic P2Y/P2U-purinoceptors at the RPE apical membrane and implicate extracellular ATP in vivo as a retinal signaling molecule that could help regulate the hydration and chemical composition of the subretinal space.