Control of excitatory synaptic transmission by capsaicin is unaltered in TRPV1 vanilloid receptor knockout mice - PubMed (original) (raw)

Control of excitatory synaptic transmission by capsaicin is unaltered in TRPV1 vanilloid receptor knockout mice

Felix Benninger et al. Neurochem Int. 2008 Jan.

Abstract

Several studies have shown that capsaicin could effectively regulate excitatory synaptic transmission in the central nervous system, but the assumption that this effect is mediated by TRPV1 vanilloid receptors (TRPV1Rs) has not been tested directly. To provide direct evidence, we compared the effect of capsaicin on excitatory synapses in wild type mice and TRPV1R knockouts. Using whole-cell patch-clamp techniques, excitatory postsynaptic currents (EPSCs) were recorded in granule cells of the dentate gyrus. First, we investigated the effect of capsaicin on EPSCs evoked by focal stimulation of fibers in the stratum moleculare. Bath application of 10 microM capsaicin reduced the amplitude of evoked EPSCs both in wild type and TRPV1R knockout animals to a similar extent. Treatment of the slices with the TRPV1R antagonist capsazepine (10 microM) alone, or together with the agonist capsaicin, also caused a decrease in the EPSC amplitude both in wild type and TRPV1R knockout animals. Both drugs appeared to affect the efficacy of excitatory synapses at presynaptic sites, since a significant increase was observed in paired-pulse ratio of EPSC amplitude after drug treatment. Next we examined the effect of capsaicin on spontaneously occurring EPSCs. This prototypic vanilloid ligand increased the frequency of events without changing their amplitude in wild type mice. Similar enhancement in the frequency without altering the amplitude of spontaneous EPSCs was observed in TRPV1R knockout mice. These data strongly argue against the hypothesis that capsaicin modulates excitatory synaptic transmission by activating TRPV1Rs, at least in the hippocampal network.

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Figures

Fig. 1

Fig. 1

Results of genotyping a litter. Presence of a 150 bp length fragment indicates wild type allele, 300 bp PCR fragment shows targeted allele. TRPV1Rs (+/+, wild type;+/−, heterozygote; −/−, knockout). Controls (ctr) for +/+ and −/− are also indicated.

Fig. 2

Fig. 2

The suppression of excitatory postsynaptic currents by capsaicin in dentate granule cells recorded in wild type (WT) or TRPV1R knockout (KO) mice. (A): Representative averaged recordings of six to eight consecutive EPSCs taken before (black) and after application of 10 μM capsaicin (gray) in wild type mice (WT) or in TRPV1R knockouts. Scale bars are 25 pA and 10 ms. (B): Individual values (open circles) and averaged data (solid circles) for the capsaicin-induced suppression of EPSCs in wild type and TRPV1R knockout mice are shown.

Fig. 3

Fig. 3

The reduction of excitatory postsynaptic currents by capsazepine (CZ) in dentate granule cells recorded in wild type (WT) or TRPV1R knockout (KO) mice. (A): Representative averaged recordings of 8–10 consecutive EPSCs taken before (black) and after application of 10 μM capsazepine (gray) in wild type mice (WT) or in TRPV1R knockouts. Scale bars are 25 pA and 10 ms. (B): Individual values (open circles) and averaged data (solid circles) for the capsazepine-induced suppression of EPSCs in wild type and TRPV1R knockout mice are shown.

Fig. 4

Fig. 4

The occurrence of spontaneous EPSCs in dentate granule cells is increased by capsaicin both in wild type and TRPV1R knockout mice. (A): Representative raw recordings before and after bath application of 10 μM capsaicin. Scale bars are 10 pA and 100 ms. (B): Median of individual experiments (open circles) and averaged values (filled circles) for the inter-event interval (IEI) and the amplitude of spontaneous EPSCs in control and after drug application are shown. Capsaicin induced a significant reduction in the inter-event intervals of synaptic events (i.e., increased the frequency) without changing their amplitude both in wild type and TRPV1R knockout mice.

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