Enhancement of spontaneous synaptic activity in rat Purkinje neurones by ATP during development.
The establishment of functional synaptic connections and activity is a pivotal process in the development of neuronal networks. We have studied the synaptic activity in the developing rat cerebellum, and the contribution mediated by purinergic receptors. The mean frequency of the spontaneous postsynaptic currents (sPSCs) recorded with the whole-cell patch-clamp technique from Purkinje neurones in acute brain slices at room temperature, increased fourfold from 4.4+/-0.8 Hz at postnatal day 9/10 (n=23) to 17.8+/-1.6 Hz at postnatal day 17-20 (p17-p20; n=113; P<0.01). ATP, which increased the frequency of sPSCs by up to 100% (EC50=18 microM) in the third postnatal week, started to modulate the synaptic activity during the second postnatal week, which was determined by three processes: (1) the appearance of functional ATP receptors during p10-p12, (2) the enhancement of the sPSC frequency by endogenous ATP release becoming apparent after inhibition of ecto-ATPases by 6-N,N-diethyl-beta,gamma-dibromomethylene-D-adenosine-5-triphosphate (ARL67156; 50 microM) at p11-p12, and (3) with tonic stimulation of purinoceptors at p14, as revealed by the P2 receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 10 microM). ATP had a similar effect at later stages (p24-p27) and at 35 degrees C. Our results suggest that endogenous release of ATP starts to enhance the synaptic activity in Purkinje neurones by the end of the second postnatal week.
Casel
Diana
D
Abteilung Allgemeine Zoologie, Fachbereich Biologie, TU Kaiserslautern, Postfach 3049, D-67653 Kaiserslautern, Germany.
Brockhaus
Johannes
J
Deitmer
Joachim W
JW
D000200:Action Potentials / Q000187:drug effects; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002531:Cerebellum / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D011689:Purkinje Cells / Q000187:drug effects* / Q000502:physiology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D013696:Temperature; D013997:Time Factors; D015854:Up-Regulation
C092431:6-N,N-diethyl-beta,gamma-dibromomethylene-D-ATP; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; C027201:ectoATPase