Presynaptic inhibition of synaptic transmission in the rat hippocampus by activation of muscarinic receptors: involvement of presynaptic calcium influx.
1. Modulation of presynaptic voltage-dependent calcium channels (VDCCs) by muscarinic receptors at the CA3-CA1 synapse of rat hippocampal slices was investigated by using the calcium indicator fura-2. Stimulation-evoked presynaptic calcium transients ([Ca(pre)]t) and field excitatory postsynaptic potentials (fe.p.s.ps) were simultaneously recorded. The relationship between presynaptic calcium influx and synaptic transmission was studied. 2. Activation of muscarinic receptors inhibited [Ca(pre)]t, thereby reducing synaptic transmission. Carbachol (CCh, 10 microM) inhibited [Ca(pre)]t by 35% and reduced fe.p.s.p. by 85%. The inhibition was completely antagonized by 1 microM atropine. An approximate 4th power relationship was found between presynaptic calcium influx and postsynaptic responses. 3. Application of the N-type VDCC-blocking peptide toxin omega-conotoxin GVIA (omega-CTx GVIA, 1 microM) inhibited [Ca(pre)]t and fe.p.s.ps by 21% and 49%, respectively, while the P/Q-type VDCC blocker omega-agatoxin IVA (omega)-Aga IVA, 1 microM) reduced [Ca(pre)]t and fe.p.s.ps by 35% and 85%, respectively. 4. Muscarinic receptor activation differentially inhibited distinct presynaptic VDCCs. Omega-CTx GVIA-sensitive calcium channels were inhibited by muscarinic receptors, while omega-Aga IVA-sensitive channels were not. The percentage inhibition of omega-CTx GVIA-sensitive [Ca(pre)]t was about 63%. 5. Muscarinic receptors inhibited presynaptic VDCCs in a way similar to adenosine (Ad) receptors. The percentage inhibition of omega-CTx GVIA-sensitive [Ca(pre)]t by Ad (100 microM) was about 59%. There was no significant inhibition of omega-Aga IVA-sensitive channels by Ad. The inhibitions of [Ca(pre)]t by CCh and Ad were mutually occlusive. 6. These results indicate that inhibition of synaptic transmission by muscarinic receptors is mainly the consequence of a reduction of the [Ca(pre)]t due to inhibition of presynaptic VDCCs.
Qian
J
J
Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, U.S.A.
Saggau
P
P
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D016257:Fura-2 / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D066298:In Vitro Techniques; D009433:Neural Inhibition; D010455:Peptides / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013111:Spider Venoms / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D010455:Peptides; D011976:Receptors, Muscarinic; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D001285:Atropine; D002217:Carbachol; D020866:omega-Conotoxin GVIA; D002118:Calcium; D016257:Fura-2