CALCIUM CURRENTS IN TURTLE RETINAL GANGLION-CELLS .2. DOPAMINE MODULATION VIA A CYCLIC-AMP-DEPENDENT MECHANISM

1. Voltage-activated calcium currents participate in shaping the firin g pattern of neurons. Calcium currents also have a role in signal tran sduction. In the retina, little is known ofthe regulation of calcium e ntry into neurons via voltage-activated channels. In the present serie s of experiments we used standard whole cell and perforated patch clam p techniques to study the ability ofthe neurotransmitter dopamine (DA) to modulate voltage-dependent calcium currents in isolated turtle ret inal ganglion cells. 2. Two types of calcium current have been describ ed in these cells, one transient and the other sustained. Here we focu sed our studies primarily on the sustained current (I-Ca). Exogenous D A reduced I-Ca in some cells (59%), facilitated I-Ca in others (17%), or had no effect on the remainder (24%). Regardless of the action of D A, there was no effect on the voltage dependence of I-Ca. In addition, the effects were all reversible. The average magnitude of decrease wa s 43%, whereas that of increase was 75%. 3. The application of a speci fic D1 receptor agonist, SKF38393, mimicked the effect of DA. This was also true for a membrane permeable cyclic AMP (cAMP) analogue (8-CPT- cAMP). Inhibition of protein kinase A (PKA) activity by a specific inh ibitor, IP20-amide, injected into cells prevented the modulatory effec ts of DA on I-Ca. 4. Immunocytochemical studies demonstrated that DA s timulation of the retina significantly increased the level of cAMP imm unoreactivity in peripheral ganglion cells, whereas those cells in cen tral retina were less affected. Forskolin induced a general elevation of cytoplasmic cAMP staining in all ganglion cells. 5. Current clamp e xperiments were carried out to determine the role of the calcium curre nts in action potential generation. Both the sustained and transient c urrents participated in the shaping of current-induced firing patterns of isolated cells. Depolarizing current-induced spiking of ganglion c ells was found to be highly modified by dopamine. 6. These results sup port the notion that endogenous DA modulates the conductance of voltag e-dependent calcium channels in turtle retinal ganglion cells and that this modulation is mediated by a D1 dopamine receptor-cAMP-PKA pathwa y. The direct result of this modulation is an alteration in the signal ing properties of certain cells.