GABAB receptor-mediated presynaptic inhibition in guinea-pig hippocampus is caused by reduction of presynaptic Ca2+ influx.
1. The hypothesis that activation of GABAB receptors inhibits evoked synaptic transmission by reducing the presynaptic Ca2+ influx was tested using a recently developed technique for simultaneously recording the presynaptic Ca2+ transient ([Ca2+]t) and the field excitatory postsynaptic potential (fEPSP) evoked by a single electrical stimulus at CA3 to CA1 synapses of guinea-pig hippocampus. 2. The GABAB receptor agonist baclofen reversibly blocked, in a dose-dependant manner, both the fEPSP and the presynaptic [Ca2+]t with similar time courses. During application of baclofen, the fEPSP was proportional to about the fourth power of the presynaptic [Ca2+]t, and the presynaptic fibre volley and the resting Ca2+ level did not change. These results are similar to those we previously observed following application of several voltage-dependent Ca2+ channel blockers, suggesting that baclofen inhibits the fEPSP by blocking the presynaptic Ca2+ influx. 3. The inhibition by baclofen of both the fEPSP and the presynaptic [Ca2+]t was blocked by the GABAB receptor antagonist CGP 35348, consistent with the causal relationship between the GABAB receptor-mediated presynaptic inhibition of the [Ca2+]t and the fEPSP. 4. The inhibition by baclofen of the [Ca2+]t was partially occluded by application of the voltage-dependent Ca2+ channel blocker omega-conotoxin-GVIA (omega-CgTX-GVIA), but not omega-agatoxin-IVA (omega-AgaTX-IVA), suggesting that baclofen reduces the presynaptic [Ca2+]t by blocking Ca2+ channels including the omega-CgTX-GVIA-sensitive type. 5. We conclude that baclofen inhibits evoked transmitter release by reducing presynaptic Ca2+ influx.(ABSTRACT TRUNCATED AT 250 WORDS)
Wu
L G
LG
Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
Saggau
P
P
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D005470:Fluorometry; D018756:GABA Antagonists / Q000494:pharmacology; D006168:Guinea Pigs; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission
D002121:Calcium Channel Blockers; D018756:GABA Antagonists; D018080:Receptors, GABA-B; D001418:Baclofen; D002118:Calcium