Gamma-aminobutyric acid type B receptors facilitate L-type and attenuate N-type Ca(2+) currents in isolated hippocampal neurons.
Activation of presynaptic gamma-aminobutyric acid type B (GABA(B)) receptors inhibits neurotransmitter release at many synapses (both excitatory and inhibitory), and activation of postsynaptic GABA(B) receptors leads to a general inhibition of the postsynaptic cell in mature neurons. Although the action of GABA(B) receptors at the soma of excitatory hippocampal pyramidal cells has been resolved to be regulation of a potassium or calcium conductance, it is not clear that all neurons in the hippocampus demonstrate similar effects of GABA(B) receptor activation. In the current study, GABA(B) receptor-mediated effects on calcium currents in acute cultures composed of heterogeneous cells from the superior region of neonatal hippocampi were studied. In 54.5% of cells, the GABA(B) receptor agonist baclofen (10 microM) attenuated the whole-cell calcium current by 21.0% +/- 1.1%. In 29.9% of cells, baclofen facilitated the calcium current by 43.5% +/- 8.1%. The component of current attenuated by baclofen was blocked by the N-type calcium channel antagonist omega-conotoxin GVIA (3 microM). The component of current facilitated by baclofen was blocked by the L-type channel antagonist nimodipine (20 microM). For cells that showed calcium current facilitation, baclofen shifted the half-maximal activation by approximately -14 mV. The data indicate that activation of GABA(B) receptors in neurons of the superior hippocampus attenuates current through N-type channels and facilitates current through L-type channels. The two opposing effects of GABA(B) receptor activation may reflect the heterogeneity of the cultured cells or may be a developmentally regulated phenomenon.
Carter
Thomas J
TJ
Department of Biological Sciences, Marquette University, Milwaukee, Wisconsin 53201-1881, USA.
Mynlieff
Michelle
M
D000367:Age Factors; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000378:metabolism*; D018755:GABA Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007395:Interneurons / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D009553:Nimodipine / Q000494:pharmacology; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000187:drug effects / Q000378:metabolism*; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D018755:GABA Agonists; D018080:Receptors, GABA-B; D009553:Nimodipine; D020866:omega-Conotoxin GVIA; D001418:Baclofen