No abstract

Both serotonin and the selective gamma-aminobutyric acidB (GABAB) agonist, baclofen, increase potassium (K+) conductance in hippocampal pyramidal cells. Although these agonists act on separate receptors, the potassium currents evoked by the agonists are not additive, indicating that the two receptors share the same potassium channels. Experiments with hydrolysis-resistant guanosine triphosphate (GTP) and guanosine diphosphate analogs and pertussis toxin indicate that the opening of the potassium channels by serotonin and GABAB receptors involves a pertussis toxin-sensitive GTP-binding (G) protein, which may directly couple the two receptors to the potassium channel.

SUMMARY1. The actions of serotonin (5-HT) on pyramidal cells of the CAI region of the rat hippocampus were characterized using intracellular recording in in vitro brain slices.2. 5-HT typically evokes a biphasic response consisting of a hyperpolarization which is followed by a longer-lasting depolarization. These effects on membrane potential are accompanied by a decrease in the calcium-activated after-hyperpolarization (a.h.p).3. Detailed analysis using 5-HT antagonists and agonists indicates that the hyperpolarization is mediated by a 5-HTlA receptor. Spiperone is the most effective antagonist of the response and the selective 5-HTlA agonist, 8-OHDPAT, behaves as a partial agonist at this receptor. In agreement with the distribution of 5-HTlA binding sites, responses to 5-HT were most prominent in the stratum radiatum.4. The hyperpolarizing response is associated with a decrease in input resistance, is blocked by extracellular barium and intracellular caesium, is unaffected by the chloride gradient, and its reversal potential shifts with the extracellular concentration of potassium as predicted for a response mediated by a selective increase in potassium permeability.5. The depolarizing response and reduction in the a.h.p. could be studied in isolation by blocking the hyperpolarizing response with either pertussis toxin or spiperone. The pharmacology of these responses did not correspond to that of any of the 5-HT binding sites reported in C.N.S. tissue. Although the depolarization and blockade of the a.h.p. have the same time course it is unclear if they are mediated by the same or different receptors.6. The depolarization most likely results from a decrease in resting potassium conductance. However, neither a blockade of the M current nor the a.h.p. current can account for the depolarization.7. Blockade of phosphodiesterase activity by 3-isobutyl-l-methylxanthine (IBMX) did not enhance the depressant action of 5-HT on the a.h.p., making it unlikely that this action is mediated by cyclic AMP.

The developing prefrontal cortex receives a dense serotonergic innervation, yet little is known about the actions of serotonin

Transmitter release in neurons is thought to be mediated exclusively by high-voltage-activated (HVA) Ca(2+) channels. However, we now report that, in retinal bipolar cells, low-voltage-activated (LVA) Ca(2+) channels also mediate neurotransmitter release. Bipolar cells are specialized neurons that release neurotransmitter in response to graded depolarizations. Here we show that these cells express T-type Ca(2+) channel subunits and functional LVA Ca(2+) currents sensitive to mibefradil. Activation of these currents results in Ca(2+) influx into presynaptic terminals and exocytosis, which we detected as a capacitance increase in isolated terminals and the appearance of reciprocal currents in retinal slices. The involvement of T-type Ca(2+) channels in bipolar cell transmitter release may contribute to retinal information processing.