Intracellular Injection of Cyclic AMP Inhibits the Dopamine-Induced K+-Dependent Responses of Aplysia Ganglion Cells

Postganglionic parasympathetic neurons of the opossum gallbladder were studied using morphological and intracellular electrophysiological recording techniques. On average there were 17 ganglia/cm2 with 8 neurons/ganglion arranged as loosely or densely packed clusters. Intracellular injection of horseradish peroxidase identified two types of neurons. Most of the neurons (approximately 80%) had a single long process that extended beyond the ganglion border with few or no short additional neurites. The other type was multipolar, having several processes that did not appear to extend beyond the ganglion border. Gallbladder neurons had passive and active electrical properties similar to other parasympathetic ganglion cells. Most of neurons studied (71%) responded to intracellular injection of suprathreshold depolarizing current with a short burst of action potentials. The remaining neurons (29%) responded with only an initial action potential. Seventy percent of the neurons tested received nicotinic fast excitatory postsynaptic potentials (EPSPs). Nineteen percent of these neurons also exhibited a slow depolarizing response following repetitive orthodromic nerve stimulation. Cholecystokinin octapeptide sulfate (CCK-8, 0.1-500 nM) had no effect on resting membrane potential or membrane input resistance. However, CCK-8 increased the amplitude of fast EPSPs evoked by orthodromic nerve stimulation by facilitating release of acetylcholine because CCK-8 had no effect on the postsynaptic response to exogenously applied acetylcholine. These data suggest that the ganglionated plexus of the gallbladder may mediate some of the observed effects of CCK-8 on gallbladder motility.

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

Journal of Neurophysiology ◽

10.1152/jn.1994.71.2.743 ◽

1994 ◽

Vol 71 (2) ◽

pp. 743-752 ◽

Cited By ~ 30

Author(s):

Y. Liu ◽

E. M. Lasater

Keyword(s):

Cyclic Amp ◽

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Specific Inhibitor ◽

D1 Receptor ◽

Calcium Currents ◽

Direct Result ◽

Retinal Ganglion ◽

Isolated Cells ◽

Voltage Dependent

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.

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