DOPAMINE ENHANCES A GLUTAMATE-GATED IONIC CURRENT IN OFF BIPOLAR CELLS OF THE TIGER SALAMANDER RETINA

The transmitter glutamate is thought to be used by all vertebrate phot oreceptors to drive the second-order neurons of the retina, horizontal and bipolar neurons. Dopamine, an endogenous retinal neurotransmitter localized to amacrine and interplexiform cells, has previously been s hown to enhance glutamate-gated currents in retinal horizontal cells. In the present study we demonstrate that bipolar cells, like horizonta l cells, possess glutamate receptors that are modulated by dopamine. W e then identify some components of the pathway through which dopamine acts. We used whole-cell patch recording to measure how bath-applied d opamine modulated the currents elicited by puffs of transmitter soluti ons at bipolar cell dendrites. Excitatory amino acid-gated currents we re evoked by pressure ejecting 1 mM glutamate or 10 mu M kainate for 4 0 msec through a micropipette positioned at the dendrites of bipolar c ells. Bath-applied dopamine (20 mu M) enhanced the response to glutama te in OFF bipolar cells in the retinal slice by 40% and in isolated OF F bipolar cells by 65%. We also explored the components of the intrace llular pathway mediating this modulation. Response enhancement was blo cked by the D1 receptor antagonist SCH23390, but not by the D2 recepto r antagonist spiperone, suggesting that the enhancement by dopamine is mediated by a D1 receptor. GDP-beta-S, a G-protein inactivator, block ed the enhancing action of dopamine, suggesting that the D1 receptor a ctivated a G-protein to enhance the glutamate-gated current. Both 8-(4 -chloropenylthio)adenosine, a cAMP analog, and the addition of the cat alytic subunit of protein kinase A (PKA) to the recording pipette enha nced glutamate-gated currents, while H-7, a PK inactivator, and PKI(20 )amide, a PKA-specific inhibitor, blocked the enhancing action of dopa mine. These data suggest that dopamine acts at D1 receptors in the den drites of bipolar cells to activate adenyl cyclase, which through cAMP enhances a glutamate-gated current in bipolar cell dendrites. Thus, d opamine may modulate synaptic transmission from photoreceptors to OFF bipolar cells.