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The Journal of Neuroscience, 0000, 20:RC105:1-5

RAPID COMMUNICATION
Bradykinin, But Not Muscarinic, Inhibition of M-Current in Rat Sympathetic Ganglion Neurons Involves Phospholipase C-4

Jane E. Haley, Fe C. Abogadie, Jose M. Fernandez-Fernandez, Mariza Dayrell, Yvonne Vallis, Noel J. Buckley, and David A. Brown

Wellcome Laboratory for Molecular Pharmacology, Department of Pharmacology, University College London, London, WC1E 6BT, United Kingdom

Rat superior cervical ganglion (SCG) neurons express low-threshold noninactivating M-type potassium channels (I_K(M)), which can be inhibited by activation of M₁ muscarinic receptors (M₁ mAChR) and bradykinin (BK) B₂ receptors. Inhibition by the M₁ mAChR agonist oxotremorine methiodide (Oxo-M) is mediated, at least in part, by the pertussis toxin-insensitive G-protein G_q (Caulfield et al., 1994; Haley et al., 1998a), whereas BK inhibition involves G_q and/or G₁₁ (Jones et al., 1995). G_q and G₁₁ can stimulate phospholipase C- (PLC-), raising the possibility that PLC is involved in I_K(M) inhibition by Oxo-M and BK. RT-PCR and antibody staining confirmed the presence of PLC-1, -2, -3, and -4 in rat SCG. We have tested the role of two PLC isoforms (PLC-1 and PLC-4) using antisense-expression constructs. Antisense constructs, consisting of the cytomegalovirus promoter driving antisense cRNA corresponding to the 3'-untranslated regions of PLC-1 and PLC-4, were injected into the nucleus of dissociated SCG neurons. Injected cells showed reduced antibody staining for the relevant PLC- isoform when compared to uninjected cells 48 hr later. BK inhibition of I_K(M) was significantly reduced 48 hr after injection of the PLC-4, but not the PLC-1, antisense-encoding plasmid. Neither PLC- antisense altered M₁ mAChR inhibition by Oxo-M. These data support the conclusion of Cruzblanca et al. (1998) that BK, but not M₁ mAChR, inhibition of I_K(M) involves PLC and extends this finding by indicating that PLC-4 is involved.

Key words: M-current; muscarinic receptor; bradykinin; phospholipase C-; antisense; superior cervical ganglion neuron

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Copyright © 0000 Society for Neuroscience  0270-6474/00/$05.00/0

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