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Muscarinic M1 receptors activate phosphoinositide turnoverand Ca2+ mobilisation in rat sympathetic neurones, but thissignalling pathway does not mediate M-current inhibition

del Rio, E; Bevilacqua, JA; Marsh, SJ; Halley, P; Caulfield, MP; (1999) Muscarinic M1 receptors activate phosphoinositide turnoverand Ca2+ mobilisation in rat sympathetic neurones, but thissignalling pathway does not mediate M-current inhibition. The Journal of Physiology , 520 (1) 101 - 111.

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Abstract

The relationship between muscarinic receptor activation, phosphoinositide turnover, calcium mobilisation and M-current inhibition has been studied in rat superior cervical ganglion (SCG) neurones in primary culture.Phosphoinositide-specific phospholipase C (PLC) stimulation was measured by the accumulation of [3H]-cytidine monophosphate phosphatidate (CMP-PA) after incubation with [3H]-cytidine in the presence of Li+. The muscarinic agonist oxotremorine methiodide (oxo-M) stimulated PLC in a dose-dependent manner with an EC50 of approximately 3·5 µM.The concentration-response curve for oxo-M was shifted to the right by a factor of about 10 by pirenzepine (100 nM), suggesting a pKB (-log of the apparent dissociation constant) of 7·9 ± 0·4, while himbacine (1 µM) shifted the curve by a factor of about 13 (pKB ~7·1 ± 0·6). This indicates involvement of the M1 muscarinic receptor in this response.The accumulation of CMP-PA was localised by in situ autoradiography to SCG principal neurones, with no detectable signal in glial cells present in the primary cultures.The ability of oxo-M to release Ca2+ from inositol(1,4,5)trisphosphate (InsP3)-sensitive stores was determined by fura-2 microfluorimetry of SCG neurones voltage clamped in perforated patch mode. Oxo-M failed to evoke intracellular Ca2+ (Ca2+i) mobilisation in SCG neurones voltage clamped at -60 mV, but produced a significant Ca2+i rise (67 ± 15 nM, n = 9) in cells voltage clamped at -25 mV.Thapsigargin (0·5-1 µM) caused a 70 % inhibition of the oxo-M-induced Ca2+i increase, indicating its intracellular origin, while oxo-M-induced inhibition of M-current in the same cells was unaffected by thapsigargin.Our results do not support the involvement of InsP3-sensitive calcium mobilisation in M-current inhibition.

Type:Article
Title:Muscarinic M1 receptors activate phosphoinositide turnoverand Ca2+ mobilisation in rat sympathetic neurones, but thissignalling pathway does not mediate M-current inhibition
Additional information:Imported via OAI, 7:29:01 5th Jul 2005
Keywords:Receptor, phosphoinositide, rat, phosphoinositides, potassium channels, muscarinic receptors
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of)

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