The dendritic arbor of pyramidal neurons is not a monolithic structure.Weshow here that the excitability of terminal apical dendrites differs from that of the apical trunk. In response to ?uorescence-guided focal photolysis of caged glutamate, individual terminal apical dendrites generated cadmium-sensitive all-or-none responses that were subthreshold for somatic action potentials. Calcium transients produced by all-or-none responses were not restricted to the sites of photolysis, but occurred throughout individual distal dendritic compartments, indicating that electrogenesis is mediated primarily by voltagegated calcium channels. Compartmentalized and binary behavior of parallelconnected terminal dendrites can greatly expand the computational power of a single neuron.

1. Transient outward current was recorded in cultured frog melanotrophs with the whole-cell configuration of the patch-clamp technique. The ionic dependence, kinetics and pharmacological properties of the current were studied. The effects of the A1 adenosine receptor agonist R-N6 enylisopropyl-adenosine (R-PIA) on this current were also investigated. 2. In tetrodotoxin-and cobalt-containing solution, depolarization from -120 mV elicited both transient and delayed outward currents. Pulses from -60 mV activated only a sustained late current. 3. 4-Aminopyridine (4 mM) reduced the transient outward current much more than the delayed outward current. In contrast, tetraethylammonium (10-20 mM) selectively reduced the delayed current. 4. Tail current measurements showed a positive shift in the reversal potential when external K+ concentration was increased, indicating that K+ was the predominant charge carrier. 5. Steady-state inactivation was complete at potentials positive to -10 mV and removed by hyperpolarization. 6. Inactivation of the transient current was slowed and accelerated in oxidizing and reducing conditions, respectively, confirming the involvement of an inactivating 'ball and chain'peptide. 7. R-PIA increased the transient current. The steady-state inactivation curve was shifted towards more positive potentials without changing the activation kinetics. Pretreatment with pertussis toxin (1 jug ml-') blocked the response to R-PIA. 8. It is concluded that frog melanotrophs possess an A-type current that is likely to play an important role in excitability. This current, which is directly modulated by A, adenosine receptors through a Gi/Go protein, appears to be responsible for the inhibitory effects of adenosine on electrical activity.

The functions of the D 4 receptor, a newly cloned D2-1ike receptor, as well as the identity of cells expressing it, are still poorly defined. Using quantitative polymerase chain reaction we detected the messenger RNA of the D4, but not other D2-1ike receptor, in cultured granule cells from neonatal rat cerebellum. In these neurons, dopamine reduced high-voltage-activated calcium current, with a pharmacology corresponding to that of the D 4 receptor. The response declined from one to three days, when calcium currents were mostly sensitive to nifedipine, to 15 days, when nifedipine-insensitive calcium currents were also present and D 4 receptor messenger RNA had declined. The dopamine response was abolished after pretreatment of the cells by pertussis toxin, was potentiated and made irreversible by infusion of guanosine 5'-O-(3-thiotriphosphate) but persisted in the presence of cyclic AMP and isobutylmethylxanthine.

The molecular mechanisms regulating GABA, receptor activity in cultured frog rnelanotrophs were studied using the patch-clamp technique. In the whole-cell configuration, application of GABA evoked a dose-related increase of inward chloride currents. The ED, value, estimated from the sigmoidal dose-response curve was 2 x M and the Hill coefficient was 1.55. The amplitude of the GABA-induced current decayed with time, Kinetics analysis of the desensitization revealed that the time-course of the current decrement was fitted by one exponential. Graded doses of GABA or association of GABA with the benzodiazepine receptor agonist flunitrazepam accelerated the desensitization process. In contrast, the time-course of the current did not significantly vary at different holding potentials. In the outside-out configuration, GABA was found to activate channels which displayed three unitary conductance levels (8, 15 and 30 pS). The channel openings of the more frequent conductance level (30 pS) exhibited short and long lasting open states (1.2 and 28.3 ms at -60mV). Altogether these data reveal that frog melanotrophs possess a single population of GABA, receptors which interconvert into a higher affinity state in the presence of benzodiazepine receptor agonists. Two GABA molecules must bind to the receptor to trigger long lasting channel openings. In addition, the activity of the GABA,receptor appears to be independent of the accumulation of intracellular chloride ions.