Calcium currents in turtle retinal ganglion cells. II. Dopamine modulation via a cyclic AMP-dependent mechanism

1. Voltage-activated calcium currents participate in shaping the firing pattern of neurons. Calcium currents also have a role in signal transduction. In the retina, little is known of the regulation of calcium entry into neurons via voltage-activated channels. In the present series of experiments we used standard whole cell and perforated patch clamp techniques to study the ability of the neurotransmitter dopamine (DA) to modulate voltage-dependent calcium currents in isolated turtle retinal ganglion cells. 2. Two types of calcium current have been described in these cells, one transient and the other sustained. Here we focused our studies primarily on the sustained current (ICa). Exogenous DA reduced ICa in some cells (59%), facilitated ICa in others (17%), or had no effect on the remainder (24%). Regardless of the action of DA, there was no effect on the voltage dependence of ICa. In addition, the effects were all reversible. The average magnitude of decrease was 43%, whereas that of increase was 75%. 3. The application of a specific 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 inhibitor, IP20-amide, injected into cells prevented the modulatory effects of DA on ICa. 4. Immunocytochemical studies demonstrated that DA stimulation of the retina significantly increased the level of cAMP immunoreactivity in peripheral ganglion cells, whereas those cells in central retina were less affected. Forskolin induced a general elevation of cytoplasmic cAMP staining in all ganglion cells. 5. Current clamp experiments were carried out to determine the role of the calcium currents in action potential generation. Both the sustained and transient currents participated in the shaping of current-induced firing patterns of isolated cells. Depolarizing current-induced spiking of ganglion cells was found to be highly modified by dopamine. 6. These results support the notion that endogenous DA modulates the conductance of voltage-dependent calcium channels in turtle retinal ganglion cells and that this modulation is mediated by a D1 dopamine receptor-cAMP-PKA pathway. The direct result of this modulation is an alteration in the signaling properties of certain cells.