Presynaptic inhibition of synaptic transmission in the rat hippocampus by activation of muscarinic receptors: involvement of presynaptic calcium influx |
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Authors: | Jing Qian Peter Saggau |
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Affiliation: | Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, U.S.A |
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Abstract: | - 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 ([Capre]t) and field excitatory postsynaptic potentials (fe.p.s.ps) were simultaneously recorded. The relationship between presynaptic calcium influx and synaptic transmission was studied.
- Activation of muscarinic receptors inhibited [Capre]t, thereby reducing synaptic transmission. Carbachol (CCh, 10 μM) inhibited [Capre]t by 35% and reduced fe.p.s.p. by 85%. The inhibition was completely antagonized by 1 μM atropine. An approximate 4th power relationship was found between presynaptic calcium influx and postsynaptic responses.
- Application of the N-type VDCC-blocking peptide toxin ω-conotoxin GVIA (ω-CTx GVIA, 1 μM) inhibited [Capre]t and fe.p.s.ps by 21% and 49%, respectively, while the P/Q-type VDCC blocker ω-agatoxin IVA (ω-Aga IVA, 1 μM) reduced [Capre]t and fe.p.s.ps by 35% and 85%, respectively.
- Muscarinic receptor activation differentially inhibited distinct presynaptic VDCCs. ω-CTx GVIA-sensitive calcium channels were inhibited by muscarinic receptors, while ω-Aga IVA-sensitive channels were not. The percentage inhibition of ω-CTx GVIA-sensitive [Capre]t was about 63%.
- Muscarinic receptors inhibited presynaptic VDCCs in a way similar to adenosine (Ad) receptors. The percentage inhibition of ω-CTx GVIA-sensitive [Capre]t by Ad (100 μM) was about 59%. There was no significant inhibition of ω-Aga IVA-sensitive channels by Ad. The inhibitions of [Capre]t by CCh and Ad were mutually occlusive.
- These results indicate that inhibition of synaptic transmission by muscarinic receptors is mainly the consequence of a reduction of the [Capre]t due to inhibition of presynaptic VDCCs.
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Keywords: | Synaptic transmission presynaptic inhibition voltage-dependent calcium channel presynaptic muscarinic receptor modulation of synaptic transmission |
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