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Adrenergic and cholinergic inhibition of Ca2+ channels mediated by different GTP-binding proteins in rat sympathetic neurones

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Abstract

Effects of acetylcholine (ACh) and noradrenaline (NA) on voltage-gated ion channels of sympathetic neurones acutely dissociated from rat superior cervical ganglion (SCG) were examined using the whole-cell voltage-clamp technique. Depolarizing voltage steps elicited two types of low- and high-voltage-activated (LVA and HVA) Ca2+ currents. Pressure applications of ACh and NA produced concentration-dependent inhibition of the HVA Ca2+ current without affecting the LVA Ca2+ current. The inhibitory action of ACh on the Ca2+ current was blocked by a muscarinic antagonist, atropine. The action of NA was suppressed by an α 2-adrenergic antagonist, yohimbine, but not by an α 1-adrenergic antagonist, prazosin. Delayed rectifying outward K+ currents and inward rectifying K+ current were not affected by either ACh or NA. Tetrodotoxin-sensitive and -insensitive Na+ currents also remained unaffected under actions of ACh and NA. When recorded with electrode containing guanosine-5′-O-(3-thiotriphosphate) (GTP-γ-S), the inhibitory actions of ACh and NA on Ca2+ currents became irreversible. After treatment of SCG neurones with pertussis toxin, the inhibitory action of ACh on the Ca2+ current was almost completely abolished, whereas the action of NA was only partially reduced. The results suggest that ACh and NA differentially inhibit the HVA Ca2+ current via different G proteins coupling muscarinic and α 2-adrenergic receptors to Ca2+ channels in rat SCG neurones.

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References

  • Andrade R, Malenka RC, Nicoll RA (1986) A G protein couples serotonin and GABAB receptors to the same channels in hippocampus. Science 243:1261–1265

    Google Scholar 

  • Aosaki T, Kasai H (1989) Characterization of two kinds of high-voltage-activated Ca-channel currents in chick sensory neurons. Differential sensitivity to dihydropyridines and ω-conotoxin GVIA. Pflügers Arch 414:150–156

    Google Scholar 

  • Carbone E, Lux HD (1987) Kinetics and selectivity of a low-voltage-activated calcium current in chick and rat sensory neurones. J Physiol (Lond) 386:547–570

    Google Scholar 

  • Cockcroft S (1987) Polyphosphoinositide phosphodiesterase: regulation by a novel guanine nucleotide binding protein, GP. Trends Pharmacol Sci 12:75–78

    Google Scholar 

  • Constanti A, Brown DA (1981) M-currents in voltage-clamped mammalian sympathetic neurons. Neurosci Lett 24:289–294

    Google Scholar 

  • Dunlap K, Holz GG, Rane SG (1987) G proteins as regulators of ion channel function. Trends Neurosci 10:241–244

    Google Scholar 

  • Fischmeister R, Hartzell HC (1986) Mechanism of action of acetylcholine on calcium current in single cells from frog ventricle. J Physiol (Lond) 376:183–202

    Google Scholar 

  • Fox AP, Nowycky MC, Tsien RW (1987) Kinetic and pharmacological properties distinguishing three types of calcium currents in chick sensory neurones. J Physiol (Lond) 394:149–172

    Google Scholar 

  • Furshpan EJ, Landis SC, Matsumoto SG, Potter DD (1986) Synaptic function in rat sympathetic neurons in mcirocultures. I. Secretion of norepinephrine and acetylcholine. J Neurosci 6:1061–1079

    Google Scholar 

  • Gray R, Johnston D (1987) Noradrenaline and β-adrenoceptor agonists increase activity of voltage-dependent calcium channels in hippocampal neurons. Nature 327:620–622

    Google Scholar 

  • Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ (1981) Improved patch-clamp techniques for high-resolution current recordings from cells and cell-free membrane patches. Pflügers Arch 391:81–100

    Google Scholar 

  • Hescheler J, Kameyama M, Trautwein W (1986) On the mechanism of muscarinic inhibition of the cardiac Ca current. Pflügers Arch 407:182–189

    Google Scholar 

  • Hockberger P, Toselli M, Swandulla D, Lux HD (1989) A diacylglycerol analogue reduces neuronal calcium currents independently of protein kinase C activation. Nature 338:340–342

    Google Scholar 

  • Holz GG, Rane SG, Dunlap K (1986) GTP-binding proteins mediate transmitter inhibition of voltage-dependent calcium channels. Nature 319:670–672

    Google Scholar 

  • Iijima T, Irisawa H, Kameyama M (1985) Membrane currents and their modification by acetylcholine in isolated single atrial cells of the guinea-pig. J Physiol (Lond) 359:485–501

    Google Scholar 

  • Kaczmarek LK (1987) The role of protein kinase C in the regulation of ion channels and neurotransmitter release. Trends Neurosci 10:30–34

    Google Scholar 

  • Katada T, Bokoch GM, Northup JK, Ui M, Gilman AG (1984) The inhibitory guanine nucleotide-binding regulatory component of adenylate cyclase. J Biol Chem 259:3568–3577

    Google Scholar 

  • Konishi S, Otsuka M (1985) Blockade of slow excitatory postsynaptic potential by substance P antagonists in guinea-pig sympathetic ganglia. J Physiol (Lond) 361:115–130

    Google Scholar 

  • Kostyuk PG, Veselovsky NS, Tsyndrenko AY (1981) Ionic currents in the somatic membrane of rat dorsal root ganglion neurons. I. Sodium currents. Neuroscience 6:;2423–2430

    Google Scholar 

  • Kurachi Y, Nakajima T, Sugimoto T (1986) On the mechanism of activation of muscarinic K+ channels by adenosine in isolated atrial cells: involvement of GTP-binding proteins. Pflügers Arch 407:264–274

    Google Scholar 

  • Langer SZ (1981) Presynaptic regulation of the release of catecholamines. Pharmacol Rev 32:337–362

    Google Scholar 

  • Levitan IB (1988) Modulation of ion channels in neurons and other cells. Ann Rev Neurosci 11:119–136

    Google Scholar 

  • Lipscombe D, Kongsamut S, Tsien RW (1989) α-Adrenergic inhibition of sympathetic neurotransmitter release mediated by modulation of N-type calcium channel gating. Nature 340:639–642

    Google Scholar 

  • Lipton SA, Kater SB (1989) Neurotransmitter regulation of neuronal outgrowth, plasticity and survival. Trends Neurosci 12:265–270

    Google Scholar 

  • McCobb DP, Best PM, Beam KG (1989) Development alters the expression of calcium currents in chick limb motoneurons. Neuron 2:1633–1643

    Google Scholar 

  • McFadzean I, Mullaney I, Brown DA, Milligan G (1989) Antibodies to the GTP binding protein, Go, antagonize noradrenaline-induced calcium current inhibition in NG108-15 hybrid cells. Neuron 3:177–182

    Google Scholar 

  • Mochida S, Kobayashi H (1988) Protein kinase C activators mimic the M2-muscarinic receptor-mediated effects on the action potential in isolated sympathetic neurons of rabbits. Neurosci Lett 86:201–206

    Google Scholar 

  • Nicoll RA (1988) The coupling of neurotransmitter receptors to ion channels in the brain. Science 241:545–551

    Google Scholar 

  • Pfaffinger PJ, Martin JM, Hunter DD, Nathanson NM, Hille B (1985) GTP-binding proteins couple cardiac muscarinic receptors to a K channel. Nature 317:536–538

    Google Scholar 

  • Rane SG, Dunlap K (1986) Kinase C activator 1,2-oleoylacetylglycerol attenuates voltage-dependent calcium current in sensory neurons. Proc Natl Acad Sci USA 77:5008–5012

    Google Scholar 

  • Rane SG, Holz GG, Dunlap K (1987) Dihydropyridine inhibition of neuronal calcium current and substance P release. Pflügers Arch 409:361–366

    Google Scholar 

  • Rane SG, Walsh M, McDonald JR, Dunlap K (1989) Specific inhibitors of protein kinase C block transmitter-induced modulation of sensory neuron calcium current. Neuron 3:239–245

    Google Scholar 

  • Schofield GG, Ikeda SR (1989) Potassium currents of acutely isolated adult rat superior cervical ganglion neurons. Brain Res 485:205–214

    Google Scholar 

  • Song S-Y, Saito K, Noguchi K, Konishi S (1989) Different GTP-binding proteins mediate regulation of calcium channels by acetylcholine and noradrenaline in rat sympathetic neurons. Brain Res 494:383–386

    Google Scholar 

  • Ui M (1984) Islet-activating proteins, pertussis toxin: a probe for functions of the inhibitory guanine nucleotide for functions of the inhibitory guanine nucleotide regulatory component of adenylate cyclase. Trends Pharmacol Sci 5:277–279

    Google Scholar 

  • Yatani A, Brown AM (1989) Rapid β-adrenergic modulation of cardiac calcium channel currents by a fast G protein pathway. Science 245:71–74

    Google Scholar 

  • Yatani A, Mattera R, Codina J, Graf R, Okabe K, Padrell E, Iyengar R, Brown AM, Birnbaumer L (1988) The G protein-gated atrial K+ channel is stimulated by three distinct Gi α-subunits. Nature 336:680–682

    Google Scholar 

  • Yoshida S, Matsuda Y, Samejima A (1978) Tetrodotoxin-resistant sodium and calcium components of action potentials in dorsal root ganglion cells of the adult mouse. J Neurophysiol 41:1096–1106

    Google Scholar 

  • Wanke E, Ferroni A, Malgaroli A, Ambrosini A, Pozzan T, Meldolesi J (1987) Activation of a muscarinic receptor selectively inhibits a rapidly inactivated Ca2+ current in rat sympathetic neurons. Proc Natl Acad Sci USA 84:4313–4317

    Google Scholar 

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Song, S.Y., Saito, K., Noguchi, K. et al. Adrenergic and cholinergic inhibition of Ca2+ channels mediated by different GTP-binding proteins in rat sympathetic neurones. Pflügers Arch 418, 592–600 (1991). https://doi.org/10.1007/BF00370576

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  • DOI: https://doi.org/10.1007/BF00370576

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