Abstract
Dopamine can regulate signal generation and transmission by activating multiple receptors and signaling cascades, especially in striatum, hippocampus, and cerebral cortex. Dopamine modulates an even larger variety of cellular properties in retina, yet has been reported to do so by only D1 receptor-driven cyclic adenosine monophosphate (cAMP) increases or D2 receptor-driven cAMP decreases. Here, we test the possibility that dopamine operates differently on retinal ganglion cells, because the ganglion cell layer binds D1 and D2 receptor ligands, and displays changes in signaling components other than cAMP under illumination that should release dopamine. In adult rat retinal ganglion cells, based on patch-clamp recordings, Ca2+ imaging, and immunohistochemistry, we find that 1) spike firing is inhibited by dopamine and SKF 83959 (an agonist that does not activate homomeric D1 receptors or alter cAMP levels in other systems); 2) D1 and D2 receptor antagonists (SCH 23390, eticlopride, raclopride) counteract these effects; 3) these antagonists also block light-induced rises in cAMP, light-induced activation of Ca2+/calmodulin-dependent protein kinase II, and dopamine-induced Ca2+ influx; and 4) the Ca2+ rise is markedly reduced by removing extracellular Ca2+ and by an IP3 receptor antagonist (2-APB). These results provide the first evidence that dopamine activates a receptor in adult mammalian retinal neurons that is distinct from classical D1 and D2 receptors, and that dopamine can activate mechanisms in addition to cAMP and cAMP-dependent protein kinase to modulate retinal ganglion cell excitability.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 4032-4049 |
| Number of pages | 18 |
| Journal | Journal of Comparative Neurology |
| Volume | 520 |
| Issue number | 17 |
| DOIs | |
| State | Published - Dec 1 2012 |
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Keywords
- Ca
- CaMKII
- CAMP
- Dopamine
- Excitability
- Immunohistochemistry
- Retina
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Dopamine and full-field illumination activate D1 and D2-D5-type receptors in adult rat retinal ganglion cells. / Ogata, Genki; Stradleigh, Tyler W.; Partida, Gloria J.; Ishida, Andrew.
In: Journal of Comparative Neurology, Vol. 520, No. 17, 01.12.2012, p. 4032-4049.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Dopamine and full-field illumination activate D1 and D2-D5-type receptors in adult rat retinal ganglion cells
AU - Ogata, Genki
AU - Stradleigh, Tyler W.
AU - Partida, Gloria J.
AU - Ishida, Andrew
PY - 2012/12/1
Y1 - 2012/12/1
N2 - Dopamine can regulate signal generation and transmission by activating multiple receptors and signaling cascades, especially in striatum, hippocampus, and cerebral cortex. Dopamine modulates an even larger variety of cellular properties in retina, yet has been reported to do so by only D1 receptor-driven cyclic adenosine monophosphate (cAMP) increases or D2 receptor-driven cAMP decreases. Here, we test the possibility that dopamine operates differently on retinal ganglion cells, because the ganglion cell layer binds D1 and D2 receptor ligands, and displays changes in signaling components other than cAMP under illumination that should release dopamine. In adult rat retinal ganglion cells, based on patch-clamp recordings, Ca2+ imaging, and immunohistochemistry, we find that 1) spike firing is inhibited by dopamine and SKF 83959 (an agonist that does not activate homomeric D1 receptors or alter cAMP levels in other systems); 2) D1 and D2 receptor antagonists (SCH 23390, eticlopride, raclopride) counteract these effects; 3) these antagonists also block light-induced rises in cAMP, light-induced activation of Ca2+/calmodulin-dependent protein kinase II, and dopamine-induced Ca2+ influx; and 4) the Ca2+ rise is markedly reduced by removing extracellular Ca2+ and by an IP3 receptor antagonist (2-APB). These results provide the first evidence that dopamine activates a receptor in adult mammalian retinal neurons that is distinct from classical D1 and D2 receptors, and that dopamine can activate mechanisms in addition to cAMP and cAMP-dependent protein kinase to modulate retinal ganglion cell excitability.
AB - Dopamine can regulate signal generation and transmission by activating multiple receptors and signaling cascades, especially in striatum, hippocampus, and cerebral cortex. Dopamine modulates an even larger variety of cellular properties in retina, yet has been reported to do so by only D1 receptor-driven cyclic adenosine monophosphate (cAMP) increases or D2 receptor-driven cAMP decreases. Here, we test the possibility that dopamine operates differently on retinal ganglion cells, because the ganglion cell layer binds D1 and D2 receptor ligands, and displays changes in signaling components other than cAMP under illumination that should release dopamine. In adult rat retinal ganglion cells, based on patch-clamp recordings, Ca2+ imaging, and immunohistochemistry, we find that 1) spike firing is inhibited by dopamine and SKF 83959 (an agonist that does not activate homomeric D1 receptors or alter cAMP levels in other systems); 2) D1 and D2 receptor antagonists (SCH 23390, eticlopride, raclopride) counteract these effects; 3) these antagonists also block light-induced rises in cAMP, light-induced activation of Ca2+/calmodulin-dependent protein kinase II, and dopamine-induced Ca2+ influx; and 4) the Ca2+ rise is markedly reduced by removing extracellular Ca2+ and by an IP3 receptor antagonist (2-APB). These results provide the first evidence that dopamine activates a receptor in adult mammalian retinal neurons that is distinct from classical D1 and D2 receptors, and that dopamine can activate mechanisms in addition to cAMP and cAMP-dependent protein kinase to modulate retinal ganglion cell excitability.
KW - Ca
KW - CaMKII
KW - CAMP
KW - Dopamine
KW - Excitability
KW - Immunohistochemistry
KW - Retina
UR - http://www.scopus.com/inward/record.url?scp=84867116491&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84867116491&partnerID=8YFLogxK
U2 - 10.1002/cne.23159
DO - 10.1002/cne.23159
M3 - Article
C2 - 22678972
AN - SCOPUS:84867116491
VL - 520
SP - 4032
EP - 4049
JO - Journal of Comparative Neurology
JF - Journal of Comparative Neurology
SN - 0021-9967
IS - 17
ER -