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J Physiol Volume 564, Number 2, 465-474, April 15, 2005 DOI: 10.1113/jphysiol.2005.084012
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Developmental changes in expression of GABAA receptor-channels in rat intrinsic cardiac ganglion neurones

Harald Fischer1, Alexander A Harper2, Colin R Anderson3 and David J Adams1

1 School of Biomedical Sciences, University of Queensland, Brisbane QLD 4072, Australia
2 Division of Molecular Physiology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
3 Department of Anatomy and Cell Biology, University of Melbourne, Parkville, VIC 3010, Australia

The effects of {gamma}-aminobutyric acid (GABA) on the electrophysiological properties of intracardiac neurones were investigated in the intracardiac ganglion plexus in situ and in dissociated neurones from neonatal, juvenile and adult rat hearts. Focal application of GABA evoked a depolarizing, excitatory response in both intact and dissociated intracardiac ganglion neurones. Under voltage clamp, both GABA and muscimol elicited inward currents at –60 mV in a concentration-dependent manner. The fast, desensitizing currents were mimicked by the GABAA receptor agonists muscimol and taurine, and inhibited by the GABAA receptor antagonists, bicuculline and picrotoxin. The GABAA0 antagonist (1,2,5,6-tetrahydropyridin-4-yl)methyl phosphonic acid (TPMPA), had no effect on GABA-induced currents, suggesting that GABAA receptor-channels mediate the response. The GABA-evoked current amplitude recorded from dissociated neurones was age dependent whereby the peak current density measured at –100 mV was ~20 times higher for intracardiac neurones obtained from neonatal rats (P2–5) compared with adult rats (P45–49). The decrease in GABA sensitivity occurred during the first two postnatal weeks and coincides with maturation of the sympathetic innervation of the rat heart. Immunohistochemical staining using antibodies against GABA demonstrate the presence of GABA in the intracardiac ganglion plexus of the neonatal rat heart. Taken together, these results suggest that GABA and taurine may act as modulators of neurotransmission and cardiac function in the developing mammalian intrinsic cardiac nervous system.

(Received 28 January 2005; accepted after revision 21 February 2005; first published online 24 February 2005)
Corresponding author D. J. Adams: School of Biomedical Sciences, University of Queensland, Brisbane QLD 4072, Australia. Email: dadams{at}uq.edu.au




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