An antisense investigation of the role of the gamma-aminobutyric acidB1 receptor subunit in Ca2+ channel modulation in rat sensory neurones.
Activation of gamma-aminobutyric acid(B) (GABA(B)) receptors in dorsal root ganglion (DRG) neurones leads to inhibition of calcium (Ca(2+)) channels. The role of the GABA(B1) receptor subunit was assessed by its depletion achieved by microinjection of DRG neurones with an antisense (A/S) oligodeoxynucleotide (ODN). Control neurones were injected with a scrambled version of the A/S ODN (missense) or were not injected. Patch clamp recordings of Ca(2+) channel current were made two to four days after injection. GABA(B1) A/S substantially reduced the current inhibition induced by baclofen, a GABA(B) agonist. Therefore, most, if not all, native GABA(B) receptors which couple to Ca(2+) channels contain GABA(B1). Moreover, if native receptors are heterodimers of GABA(B1) and GABA(B2), then GABA(B2), in isolation, is unable to sustain coupling to Ca(2+) channels.
Department of Pharmacology, Division of Neuroscience, The Medical School, University of Birmingham, Edgbaston, B15 2TT, Birmingham, UK.
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Hand
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Harris
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Spruce
D000818:Animals; D016375:Antisense Elements (Genetics) / Q000494:pharmacology*; D015220:Calcium Channels / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D018080:Receptors, GABA-B / Q000235:genetics / Q000502:physiology*
D016375:Antisense Elements (Genetics); D015220:Calcium Channels; D018080:Receptors, GABA-B