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Depolarizing GABAergic synaptic input triggers endocannabinoid-mediated retrograde synaptic signaling.
Synapse. 2009 Aug; 63(8):643-52.S

Abstract

Endocannabinoids released by postsynaptic neurons inhibit neurotransmitter release from presynaptic axon terminals. One typical stimulus of endocannabinoid production is an increase of calcium concentration in postsynaptic neurons. The aim of the present study was to clarify whether depolarizing GABAergic synaptic input, by increasing calcium concentration in postsynaptic neurons, can trigger endocannabinoid production. Spontaneous GABAergic inhibitory postsynaptic currents (sIPSCs) were recorded in Purkinje cells in mouse cerebellar slices with patch-clamp pipettes containing 151 mM chloride (a usual recording mode). sIPSCs were depolarizing inward currents under this condition. Combined electrophysiological and fluorometric calcium imaging experiments indicated that sIPSCs frequently triggered calcium spikes. After the calcium spikes, a short-term suppression of sIPSCs occurred. This suppression was prevented by the CB(1) cannabinoid receptor antagonist rimonabant and the diacylglycerol lipase inhibitor orlistat, but not changed by URB597, an inhibitor of anandamide degradation. It is, therefore, likely that CB(1) receptors and 2-arachidonoylglycerol were involved. For testing the physiological significance of the above observation, we carried out experiments on brains of 3- to 5-day-old mice. The gramicidin-induced perforated patch-clamp mode was used for preserving the physiological intracellular chloride concentration of the neurons. Depolarizing GABAergic sIPSCs occurred under this condition, but at a very low rate. Rimonabant did not change the frequency of these sIPSCs, arguing against the persistence of an endocannabinoid tone. The results point to a new kind of trigger of endocannabinoid production: depolarizing GABAergic synaptic input can elicit endocannabinoid production in postsynaptic neurons by activating calcium channels. The produced endocannabinoid suppresses GABA release from presynaptic axon terminals.

Authors+Show Affiliations

Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Albert-Ludwigs-Universität, Freiburg i Br, Germany.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19347961

Citation

Urbanski, Michael J., et al. "Depolarizing GABAergic Synaptic Input Triggers Endocannabinoid-mediated Retrograde Synaptic Signaling." Synapse (New York, N.Y.), vol. 63, no. 8, 2009, pp. 643-52.
Urbanski MJ, Kovacs FE, Szabo B. Depolarizing GABAergic synaptic input triggers endocannabinoid-mediated retrograde synaptic signaling. Synapse. 2009;63(8):643-52.
Urbanski, M. J., Kovacs, F. E., & Szabo, B. (2009). Depolarizing GABAergic synaptic input triggers endocannabinoid-mediated retrograde synaptic signaling. Synapse (New York, N.Y.), 63(8), 643-52. https://doi.org/10.1002/syn.20641
Urbanski MJ, Kovacs FE, Szabo B. Depolarizing GABAergic Synaptic Input Triggers Endocannabinoid-mediated Retrograde Synaptic Signaling. Synapse. 2009;63(8):643-52. PubMed PMID: 19347961.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Depolarizing GABAergic synaptic input triggers endocannabinoid-mediated retrograde synaptic signaling. AU - Urbanski,Michael J, AU - Kovacs,Flora E, AU - Szabo,Bela, PY - 2009/4/7/entrez PY - 2009/4/7/pubmed PY - 2009/8/20/medline SP - 643 EP - 52 JF - Synapse (New York, N.Y.) JO - Synapse VL - 63 IS - 8 N2 - Endocannabinoids released by postsynaptic neurons inhibit neurotransmitter release from presynaptic axon terminals. One typical stimulus of endocannabinoid production is an increase of calcium concentration in postsynaptic neurons. The aim of the present study was to clarify whether depolarizing GABAergic synaptic input, by increasing calcium concentration in postsynaptic neurons, can trigger endocannabinoid production. Spontaneous GABAergic inhibitory postsynaptic currents (sIPSCs) were recorded in Purkinje cells in mouse cerebellar slices with patch-clamp pipettes containing 151 mM chloride (a usual recording mode). sIPSCs were depolarizing inward currents under this condition. Combined electrophysiological and fluorometric calcium imaging experiments indicated that sIPSCs frequently triggered calcium spikes. After the calcium spikes, a short-term suppression of sIPSCs occurred. This suppression was prevented by the CB(1) cannabinoid receptor antagonist rimonabant and the diacylglycerol lipase inhibitor orlistat, but not changed by URB597, an inhibitor of anandamide degradation. It is, therefore, likely that CB(1) receptors and 2-arachidonoylglycerol were involved. For testing the physiological significance of the above observation, we carried out experiments on brains of 3- to 5-day-old mice. The gramicidin-induced perforated patch-clamp mode was used for preserving the physiological intracellular chloride concentration of the neurons. Depolarizing GABAergic sIPSCs occurred under this condition, but at a very low rate. Rimonabant did not change the frequency of these sIPSCs, arguing against the persistence of an endocannabinoid tone. The results point to a new kind of trigger of endocannabinoid production: depolarizing GABAergic synaptic input can elicit endocannabinoid production in postsynaptic neurons by activating calcium channels. The produced endocannabinoid suppresses GABA release from presynaptic axon terminals. SN - 1098-2396 UR - https://www.unboundmedicine.com/medline/citation/19347961/Depolarizing_GABAergic_synaptic_input_triggers_endocannabinoid_mediated_retrograde_synaptic_signaling_ L2 - https://doi.org/10.1002/syn.20641 DB - PRIME DP - Unbound Medicine ER -