GABAB receptor‐mediated inhibition of Ca2+ currents and synaptic transmission in cultured rat hippocampal neurones.

K. P. Scholz*, R. J. Miller

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

146 Scopus citations

Abstract

1. The effects of activation of GABAB receptors on Ca2+ currents (ICa) were investigated by application of whole‐cell patch‐clamp techniques to pyramidal neurones and non‐pyramidal interneurones from the rat hippocampus grown in cell culture. 2. (+/‐)‐Baclofen (10 microM) reduced ICa evoked in pyramidal neurones at 0 mV from a holding potential of ‐80 mV by 33 +/‐ 3%. Inhibition could be observed at the peak of ICa with significant inhibition still present after 200 ms at 0 mV. When Ba2+ was used as the charge carrier (IBa) baclofen inhibited 28 +/‐ 3% of the current at ‐20 mV from a holding potential of ‐80 mV. The GABAB receptor antagonist 2‐OH‐saclofen (50‐200 microM) blocked the actions of baclofen. 3. The selective Ca2+ channel blocker, omega‐conotoxin fraction GVIA (omega‐CgTX), was used to characterize the Ca2+ currents inhibited by baclofen. omega‐CgTX (5 microM) blocked 24 +/‐ 3% of IBa. Following block of the omega‐CgTX‐sensitive current, baclofen inhibited significantly less current than under control conditions. 4. Addition of the dihydropyridine Ca2+ channel antagonist nimodipine (1 microM) inhibited 18 +/‐ 5% of ICa at 0 mV from a holding potential of ‐80 mV and 44 +/‐ 9% from a holding potential of ‐40 mV. In addition, nimodipine partially occluded subsequent responses to application of baclofen. 5. In the presence of both 5 microM‐omega‐CgTX and 200 nM‐nimodipine, responses to baclofen were almost completely blocked at depolarized holding potentials where the dihydropyridines are most effective. 6. Inclusion of 500 microM‐guanosine 5'‐O‐(3‐thiotriphosphate) (GTP‐gamma‐S) in the patch pipette enhanced the response to a subsaturating concentration of baclofen and rendered the response irreversible. Subsequent addition of the adenosine receptor agonist 2‐Cl‐adenosine (2‐CA) (1 microM; which also reduces ICa under control conditions) was without effect, suggesting that these two receptor‐effector pathways converge. 7. The actions of baclofen on ICa were blocked by pre‐treatment of the cultures with pertussis toxin (250 ng/ml). 8. Baclofen also inhibited ICa in non‐pyramidal neurones from the hippocampus, but was slightly less effective. 9. Baclofen reduced both excitatory‐ and inhibitory postsynaptic currents (EPSCs and IPSCs) recorded as a consequence of extracellular stimulation of presynaptic neurones. This action was blocked by 2‐OH‐saclofen (200 microM) and also by pretreatment of the cultures with pertussis toxin.(ABSTRACT TRUNCATED AT 400 WORDS)

Original languageEnglish (US)
Pages (from-to)669-686
Number of pages18
JournalThe Journal of Physiology
Volume444
Issue number1
DOIs
StatePublished - Dec 1 1991

ASJC Scopus subject areas

  • Physiology

Fingerprint

Dive into the research topics of 'GABAB receptor‐mediated inhibition of Ca2+ currents and synaptic transmission in cultured rat hippocampal neurones.'. Together they form a unique fingerprint.

Cite this