Presynaptic Cav2.1 and Cav2.2 differentially influence release dynamics at hippocampal excitatory synapses.
Presynaptic calcium influx at most excitatory central synapses is carried by both Cav2.1 and Cav2.2 channels. The kinetics and modulation of Cav2.1 and Cav2.2 channels differ and may affect presynaptic calcium influx. We compared release dynamics at CA3/CA1 synapses in rat hippocampus after selective blockade of either channel subtype and subsequent quantal content restoration. Selective blockade of Cav2.1 channels enhanced paired-pulse facilitation, whereas blockade of Cav2.2 channels decreased it. This effect was observed at short (50 msec) but not longer (500 msec) intervals and was maintained during prolonged bursts of presynaptic activity. It did not reflect differences in the distance of the channels from the calcium sensor. The suppression of this effect by preincubation with the G(o/i)-protein inhibitor pertussis toxin suggests instead that high-frequency stimulation relieves inhibition of Cav2.2 by G(o/i), thereby increasing the number of available channels.
Scheuber
Anita
A
Institut National de la Santé et de la Recherche Médicale, Equipe Mixte 224 Cortex et Epilepsie, Centre Hospitalier Universitaire Pitié-Salpêtrière, 75013 Paris, France.
Miles
Richard
R
Poncer
Jean Christophe
JC
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000502:physiology*; D020865:Calcium Channels, P-Type / Q000187:drug effects / Q000502:physiology*; D020907:Calcium Channels, Q-Type / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors; D006624:Hippocampus / Q000378:metabolism* / Q000648:ultrastructure; D066298:In Vitro Techniques; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission
D002118:Calcium; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D019206:GTP-Binding Protein alpha Subunits, Gi-Go