Inhibition of synaptic transmission by neuropeptide Y in rat hippocampal area CA1: modulation of presynaptic Ca2+ entry - PubMed (original) (raw)

Inhibition of synaptic transmission by neuropeptide Y in rat hippocampal area CA1: modulation of presynaptic Ca2+ entry

J Qian et al. J Neurosci. 1997.

Abstract

Neuropeptide Y (NPY) agonists inhibit glutamate release by a presynaptic action at the CA3-CA1 synapse of rat hippocampus. We have examined the relationship between [Capre]t via presynaptic, voltage-dependent calcium channels (VDCCs), measured optically by using the fluorescent calcium indicator fura-2, and transmitter release, measured electrophysiologically. Activation of presynaptic NPY Y2 receptors reduced [Capre]t and thereby inhibited synaptic transmission. Multiple calcium channels are involved in synaptic transmission at this synapse. Activation of Y2 receptors inhibits N-type, P/Q-type, and unidentified presynaptic VDCCs. The inhibition of each of these calcium channel types contributes to the reduction of [Capre]t by Y2 receptors. Activation of adenosine receptors fully occluded the inhibition of presynaptic calcium influx by Y2 receptors but not the inhibition by GABAB receptors, suggesting a convergent action for Y2 and adenosine receptors, probably by coupling to the same G-protein.

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Figures

Fig. 1.

Fig. 1.

A nonlinear relationship exists between [Capre]t and fEPSP. A, Schematic diagram for loading calcium indicators into presynaptic terminals. Esterified (membrane-permeant) forms of fura-2 or furaptra were pressure-injected into stratum radiatum (SR), where they were taken up into CA3 axons, trapped by the action of esterases, and diffused into the remote presynaptic terminals onto CA1 neurons. Typical traces of the electrically recorded field EPSP (fEPSP), normalized transients of calcium indicator-related fluorescence (Fura), and their first derivative are shown under control conditions and during blocked synaptic transmission (CNQX+APV).B, Comparison between the peak of _ΔF/F_and the peak of the first derivative of ΔF/F.C, Semi-log plot of normalized synaptic transmission and [Capre]t versus extracellular calcium concentration, [Ca2+]o. [Capre]t was a logarithmic function of [Ca2+]o. D, Double-log plot of normalized fEPSP versus [Capre]t for each tested [Ca2+]o. The regression line has a slope of m = 4.2 (_r_2 = 0.99) for fura-2 measurement and 3.8 (_r_2 = 0.99) for furaptra, respectively.

Fig. 2.

Fig. 2.

The activation of presynaptic Y2receptors inhibits [Capre]t and fEPSP.A, Group data (n = 5) showing the time course of normalized [Capre]t and fEPSP during the application of 1 μ

m

PYY. Sample traces taken at control and during maximal action of PYY are shown in the_inset_. B, Summary data for eight experiments. Approximately 20% of [Capre]twas inhibited by application of 1 μ

m

PYY. The synaptic transmission was reduced by ∼60%. C, The presynaptic volley did not show a significant change during the application of PYY.D, Double-log plot of normalized fEPSP and [Capre]t during the peak action of PYY. Estimated power number for the inhibition of synaptic transmission by PYY was 3.9 ± 0.5 (n = 8). Similar power numbers were observed in this preparation for the action of PYY and the reduction of [Ca2+]o.

Fig. 3.

Fig. 3.

ω-CgTx GVIA does not abolish the effects of PYY.A, Group data (n = 6) showing the time course of normalized [Capre]t and fEPSP during the application of ω-CgTx GVIA (1 μ

m

) and PYY (1 μ

m

). Sample traces taken at control, after application of ω-CgTx GVIA, and during the peak effect of PYY are shown in the_inset_. B, Summary data for seven experiments. After preapplication of ω-CgTx GVIA, PYY could still inhibit [Capre]t but to a lesser extent (∼15% of control [Capre]t), whereas fEPSP was decreased to 80% of control. C, Double-log plot of normalized fEPSP and [Capre]t during application of ω-CgTx GVIA and ω-CgTx GVIA+PYY. Estimated power numbers were m = 3.5 ± 0.3 (n = 7) for the inhibition by ω-CgTx GVIA alone and m = 3.9 ± 0.4 (n = 7) for the combination of ω-CgTx GVIA and PYY. The peak responses of ω-CgTx GVIA and PYY were used to calculate the power numbers.

Fig. 4.

Fig. 4.

ω-Aga IVA and ω-CgTx MVIIC do not abolish the effects of PYY. A, Group data showing the time course of normalized [Capre]t and fEPSP during the action of ω-Aga IVA (500 n

m

) alone and together with 1 μ

m

PYY. Sample traces taken at control, after application of the calcium channel toxin, and during the peak effect of PYY are shown in the inset. B, Group data showing the time course of normalized [Capre]t and fEPSP during the action of PYY together with ω-CgTx MVIIC (1 μ

m

). Sample traces taken at control, after application of calcium channel toxins, and during peak effect of PYY are shown in the_inset_. C, Summary data for_A_. [Capre]t and synaptic transmission were reduced irreversibly by ∼34 and 80%, respectively, after application of ω-Aga IVA. PYY still inhibited [Capre]t by ∼15% of control [Capre]t after blockade of P/Q-type calcium channels, and synaptic transmission also was decreased further.D, Approximately 11% inhibition of [Capre]t was observed even after application of ω-CgTx MVIIC to stop synaptic transmission almost completely.

Fig. 5.

Fig. 5.

Activation of Y2 receptors occludes the inhibition of [Capre]t by adenosine.A, Time course of normalized [Capre]t and fEPSP illustrates the occlusion of inhibition of [Capre]t between activation of Y2 and adenosine (AD) receptors. The inhibition of [Capre]t by adenosine in the presence of PYY (1 μ

m

) was always smaller than that without activation of Y2 receptors, regardless of the concentrations of adenosine (5, 10, or 100 μ

m

).B, A saturating concentration of AD (100 μ

m

) completely abolished the inhibition of [Capre]t by PYY. C,D, Time course of normalized [Capre]t and fEPSP illustrates the partial occlusion between the activation of AD receptors and the activation of GABAB receptors by baclofen (50 μ

m

).

Fig. 6.

Fig. 6.

PYY inhibits the same percentage of [Capre]t in reduced [Ca2+]o. Shown is the time course of normalized [Capre]t and fEPSP in reduced [Ca2+]o (0.7 m

m

). Application of PYY still elicited a 23.5% inhibition of [Capre]t under these conditions. The_inset_ shows the sample traces taken under control conditions (2.5 m

m

[Ca2+]o), in the presence of 0.7 m

m

[Ca2+]o, and during the peak effect of PYY.

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