Advertisement

State-dependent modulation of sympathetic firing by α1-adrenoceptors requires constitutive PKC activity in the neonatal rat spinal cord

  • Chun-Kuei Su
    Correspondence
    Department of Biotechnology, College of Life Science, Zhaoqing University, Zhaoqing 526061, Guangdong, China.
    Affiliations
    Department of Biotechnology, College of Life Science, Zhaoqing University, Zhaoqing, Guangdong, China
    Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC
    Search for articles by this author

      Highlights

      • Intraspinal a1-adrenoceptors modulate sympathetic firing in a heterogeneous manner.
      • High basal firing activity is suppressed by a1-adrenoceptor activation.
      • Low basal firing activity is potentiated by a1-adrenoceptor activation.
      • Synchronous firing modulated by a1-adrenoceptors is synchronous state-dependent.
      • Basal firing behaviors determine the neural response to a1-adrenoceptor activation.

      Abstract

      The central adrenergic and noradrenergic neurotransmitter systems diffusively affect the operation of the spinal neural network and dynamically gauge central sympathetic outflow. Using in vitro splanchnic nerve–thoracic spinal cord preparations as an experimental model, this study examined the intraspinal α1-adrenoceptor-meidated modulation of sympathetic firing behaviors. Several sympathetic single-fiber activities were simultaneously recorded. Application of phenylephrine (Phe, an α1-adrenoceptor agonist) increased, decreased or did not affect spontaneous firing. A log-log plot of the change ratios of the average firing rates (AFR) versus their basal AFR displays a linear data distribution. Thus, the heterogeneity in α1-adrenoceptor-mediated responses is well described by a power law function. Phe-induced power-law firing modulation (plFM) was sensitive to prazosin (Prz, an α1-adrenoceptor antagonist). Heparin (Hep, a competitive IP3 receptor blocker) and chelerythrine (Che, a protein kinase C inhibitor) also caused plFM. Phe-induced plFM persisted in the presence of Hep; however, it was occluded by Che pretreatment. Pair-wise analysis of single-fiber activities revealed synchronous sympathetic discharges. Application of Phe, Hep or Che suppressed synchronous discharges in fiber pairs with apparent correlated firing (ACF) and induced or potentiated synchronous discharges in those without or with minimal ACF. Thus, the basal activities of the sympathetic preganglionic neurons participate in determining the responses mediated by the activation of α1-adrenoceptors. This deterministic factor, which is intrinsic to spinal neural networks, helps the supraspinal adrenergic and noradrenergic systems differentially control their widely distributed neural targets.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Autonomic Neuroscience: Basic and Clinical
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Abbott S.B.
        • Stornetta R.L.
        • Socolovsky C.S.
        • West G.H.
        • Guyenet P.G.
        Photostimulation of channelrhodopsin-2 expressing ventrolateral medullary neurons increases sympathetic nerve activity and blood pressure in rats.
        J. Physiol. 2009; 587: 5613-5631
        • Abbott S.B.
        • Kanbar R.
        • Bochorishvili G.
        • Coates M.B.
        • Stornetta R.L.
        • Guyenet P.G.
        C1 neurons excite locus coeruleus and A5 noradrenergic neurons along with sympathetic outflow in rats.
        J. Physiol. 2012; 590: 2897-2915
        • Andrade J.M.
        • Estévez-Pérez M.G.
        Statistical comparison of the slopes of two regression lines: a tutorial.
        Anal. Chim. Acta. 2014; 838: 1-12
        • Becchetti A.
        • Amadeo A.
        Why we forget our dreams: acetylcholine and norepinephrine in wakefulness and REM sleep.
        Behav. Brain. Sci. 2016; 39: e202
        • Beekharry C.C.
        • Gu Y.
        • Magoski N.S.
        Protein kinase C enhances electrical synaptic transmission by acting on junctional and postsynaptic Ca2+ currents.
        J. Neurosci. 2018; 38: 2796-2808
        • Bittremieux M.
        • La Rovere R.M.
        • Akl H.
        • Martines C.
        • Welkenhuyzen K.
        • Dubron K.
        • Baes M.
        • Janssens A.
        • Vandenberghe P.
        • Laurenti L.
        • Rietdorf K.
        • Morciano G.
        • Pinton P.
        • Mikoshiba K.
        • Bootman M.D.
        • Efremov D.G.
        • De Smedt H.
        • Parys J.B.
        • Bultynck G.
        Constitutive IP3 signaling underlies the sensitivity of B-cell cancers to the Bcl-2/IP3 receptor disruptor BIRD-2.
        Cell Death Differ. 2019; 26: 531-547
        • Brandwein N.J.
        • Nguyen P.V.
        A requirement for epigenetic modifications during noradrenergic stabilization of heterosynaptic LTP in the hippocampus.
        Neurobiol. Learn. Mem. 2019; 161: 72-82
        • Bruinstroop E.
        • Cano G.
        • Vanderhorst V.G.
        • Cavalcante J.C.
        • Wirth J.
        • Sena-Esteves M.
        • Saper C.B.
        Spinal projections of the A5, A6 (locus coeruleus), and A7 noradrenergic cell groups in rats.
        J. Comp. Neurol. 2012; 520: 1985-2001
        • Burke P.G.
        • Abbott S.B.
        • Coates M.B.
        • Viar K.E.
        • Stornetta R.L.
        • Guyenet P.G.
        Optogenetic stimulation of adrenergic C1 neurons causes sleep state-dependent cardiorespiratory stimulation and arousal with sighs in rats.
        Am. J. Respir. Crit. Care Med. 2014; 190: 1301-1310
        • Cano G.
        • Sved A.F.
        • Rinaman L.
        • Rabin B.S.
        • Card J.P.
        Characterization of the central nervous system innervation of the rat spleen using viral transneuronal tracing.
        J. Comp. Neurol. 2001; 439: 1-18
        • Card J.P.
        • Sved J.C.
        • Craig B.
        • Raizada M.
        • Vazquez J.
        • Sved A.F.
        Efferent projections of rat rostroventrolateral medulla C1 catecholamine neurons: implications for the central control of cardiovascular regulation.
        J. Comp. Neurol. 2006; 499: 840-859
        • Cardenas C.
        • Miller R.A.
        • Smith I.
        • Bui T.
        • Molgo J.
        • Muller M.
        • Vais H.
        • Cheung K.H.
        • Yang J.
        • Parker I.
        • Thompson C.B.
        • Birnbaum M.J.
        • Hallows K.R.
        • Foskett J.K.
        Essential regulation of cell bioenergetics by constitutive InsP3 receptor Ca2+ transfer to mitochondria.
        Cell. 2010; 142: 270-283
        • Carter T.D.
        • Chen X.Y.
        • Carlile G.
        • Kalapothakis E.
        • Ogden D.
        • Evans W.H.
        Porcine aortic endothelial gap junctions: identification and permeation by caged InsP3.
        J. Cell Sci. 1996; 109: 1765-1773
        • Carvalho A.L.
        • Duarte C.B.
        • Faro C.J.
        • Carvalho A.P.
        • Pires E.V.
        Calcium influx through AMPA receptors and through calcium channels is regulated by protein kinase C in cultured retina amacrine-like cells.
        J. Neurochem. 1998; 70: 2112-2119
        • Castro-Alamancos M.A.
        • Gulati T.
        Neuromodulators produce distinct activated states in neocortex.
        J. Neurosci. 2014; 34: 12353-12367
        • Clewett D.V.
        • Huang R.
        • Velasco R.
        • Lee T.H.
        • Mather M.
        Locus coeruleus activity strengthens prioritized memories under arousal.
        J. Neurosci. Methods. 2018; 38: 1558-1574
        • Danneman P.J.
        • Mandrell T.D.
        Evaluation of five agents/methods for anesthesia of neonatal rats.
        Lab. Anim. Sci. 1997; 47: 386-395
        • Dickinson G.D.
        • Ellefsen K.L.
        • Dawson S.P.
        • Pearson J.E.
        • Parker I.
        Hindered cytoplasmic diffusion of inositol trisphosphate restricts its cellular range of action.
        Sci. Signal. 2016; 9: ra108
        • Guyenet P.G.
        • Cabot J.B.
        Inhibition of sympathetic preganglionic neurons by catecholamines and clonidine: mediation by an alpha-adrenergic receptor.
        J. Neurosci. 1981; 1: 908-917
        • Herbert J.M.
        • Augereau J.M.
        • Gleye J.
        • Maffrand J.P.
        Chelerythrine is a potent and specific inhibitor of protein kinase C.
        Biochem. Biophys. Res. Commun. 1990; 172: 993-999
        • Ho C.M.
        • Chiang C.H.
        • Lee C.M.
        • Fan Y.P.
        • Su C.K.
        Glutamatergic activities in neonatal rat spinal cord heterogeneously regulate single-fiber splanchnic nerve discharge.
        Auton. Neurosci. 2013; 177: 175-180
        • Hu H.J.
        • Gereau 4th, R.W.
        ERK integrates PKA and PKC signaling in superficial dorsal horn neurons. II. Modulation of neuronal excitability.
        J. Neurophysiol. 2003; 90: 1680-1688
        • Huchet A.M.
        • Doursout M.F.
        • Chelly J.
        • Schmitt H.
        Possible role of central α1-adrenoceptors in the control of the autonomic nervous system in normotensive and spontaneously hypertensive rats.
        Eur. J. Pharmacol. 1982; 85: 239-242
        • Inokuchi H.
        • Yoshimura M.
        • Polosa C.
        • Nishi S.
        Adrenergic receptors (alpha 1 and alpha 2) modulate different potassium conductances in sympathetic preganglionic neurons.
        Can. J. Physiol. Pharmacol. 1992; 70: S92-S97
        • Jabr R.I.
        • Hatch F.S.
        • Salvage S.C.
        • Orlowski A.
        • Lampe P.D.
        • Fry C.H.
        Regulation of gap junction conductance by calcineurin through Cx43 phosphorylation: implications for action potential conduction.
        Pflugers Arch. 2016; 468: 1945-1955
        • Jänig W.
        • Häbler H.J.
        Neurophysiological analysis of target-related sympathetic pathways--from animal to human: similarities and differences.
        Acta Physiol. Scand. 2003; 177: 255-274
        • Jonas E.A.
        • Kaczmarek L.K.
        Regulation of potassium channels by protein kinases.
        Curr. Opin. Neurobiol. 1996; 6: 318-323
        • Kim J.H.
        • Gangadharan G.
        • Byun J.
        • Choi E.J.
        • Lee C.J.
        • Shin H.S.
        Yin-and-yang bifurcation of opioidergic circuits for descending analgesia at the midbrain of the mouse.
        Proc. Natl. Acad. Sci. U. S. A. 2018; 115: 11078-11083
        • Lang P.M.
        • Moalem-Taylor G.
        • Tracey D.J.
        • Bostock H.
        • Grafe P.
        Activity-dependent modulation of axonal excitability in unmyelinated peripheral rat nerve fibers by the 5-HT3 serotonin receptor.
        J. Neurophysiol. 2006; 96: 2963-2971
        • Leybaert L.
        IP3, still on the move but now in the slow lane.
        Sci. Signal. 2016; 9: fs17
        • Liu Y.
        • Rodenkirch C.
        • Moskowitz N.
        • Schriver B.
        • Wang Q.
        Dynamic lateralization of pupil dilation evoked by locus coeruleus activation results from sympathetic, not parasympathetic, contributions.
        Cell Rep. 2017; 20: 3099-3112
        • Loewy A.D.
        • Mckellar S.
        • Saper C.B.
        Direct projections from the A5 catecholamine cell group to the intermediolateral cell column.
        Brain Res. 1979; 174: 309-314
        • Logan S.D.
        • Pickering A.E.
        • Gibson I.C.
        • Nolan M.F.
        • Spanswick D.
        Electrotonic coupling between rat sympathetic preganglionic neurones in vitro.
        J. Physiol. 1996; 495: 491-502
        • LoPachin R.M.
        • Rudy T.A.
        The effects of intrathecal sympathomimetic agents on neural activity in the lumbar sympathetic chain of rats.
        Brain Res. 1981; 224: 195-198
        • Lou X.
        • Korogod N.
        • Brose N.
        • Schneggenburger R.
        Phorbol esters modulate spontaneous and Ca2+-evoked transmitter release via acting on both Munc13 and protein kinase C.
        J. Neurosci. 2008; 28: 8257-8267
        • Maiorov D.N.
        • Wilton E.R.
        • Badoer E.
        • Petrie D.
        • Head G.A.
        • Malpas S.C.
        Sympathetic response to stimulation of the pontine A5 region in conscious rabbits.
        Brain Res. 1999; 815: 227-236
        • Marks S.A.
        • Gilbey M.P.
        Effect on cardiac sympathetic nerve activity of phenylephrine microinjected into the cat intermediolateral cell column.
        J. Physiol. 1992; 453: 185-195
        • Metzen M.G.
        • Chacron M.J.
        Neural heterogeneities determine response characteristics to second-, but not first-order stimulus features.
        J. Neurosci. 2015; 35: 3124-3138
        • Minoura Y.
        • Onimaru H.
        • Iigaya K.
        • Kobayashi Y.
        Modulation of sympathetic preganglionic neuron activity via adrenergic receptors.
        Hypertens. Res. 2018; 41: 499-505
        • Muyderman H.
        • Nilsson M.
        • Blomstrand F.
        • Khatibi S.
        • Olsson T.
        • Hansson E.
        • Ronnback L.
        Modulation of mechanically induced calcium waves in hippocampal astroglial cells. Inhibitory effects of alpha 1-adrenergic stimulation.
        Brain Res. 1998; 793: 127-135
        • Nolan M.F.
        • Logan S.D.
        • Spanswick D.
        Electrophysiological properties of electrical synapses between rat sympathetic preganglionic neurones in vitro.
        J. Physiol. 1999; 519: 753-764
        • Nuriya M.
        • Morita A.
        • Shinotsuka T.
        • Yamada T.
        • Yasui M.
        Norepinephrine induces rapid and long-lasting phosphorylation and redistribution of connexin 43 in cortical astrocytes.
        Biochem. Biophys. Res. Commun. 2018; 504: 690-697
        • Nygren L.G.
        • Olson L.
        A new major projection from locus coeruleus: the main source of noradrenergic nerve terminals in the ventral and dorsal columns of the spinal cord.
        Brain Res. 1977; 132: 85-93
        • O'Dell T.J.
        • Connor S.A.
        • Guglietta R.
        • Nguyen P.V.
        beta-Adrenergic receptor signaling and modulation of long-term potentiation in the mammalian hippocampus.
        Learn. Mem. 2015; 22: 461-471
      1. Oleskevich, S., Walmsley, B., 2000. Phosphorylation regulates spontaneous and evoked transmitter release at a giant terminal in the rat auditory brainstem. J. Physiol. 526 Pt 2, 349–57.

        • Reis D.J.
        • Ruggiero D.A.
        • Morrison S.F.
        The C1 area of the rostral ventrolateral medulla oblongata. A critical brainstem region for control of resting and reflex integration of arterial pressure.
        Am. J. Hypertens. 1989; 2: 363S-374S
        • Samuels E.R.
        • Szabadi E.
        Functional neuroanatomy of the noradrenergic locus coeruleus: its roles in the regulation of arousal and autonomic function part II: physiological and pharmacological manipulations and pathological alterations of locus coeruleus activity in humans.
        Curr. Neuropharmacol. 2008; 6: 254-285
        • Sawynok J.
        • Reid A.
        Lesions to ascending noradrenergic and serotonergic pathways modify antinociception produced by intracerebroventricular administration of morphine.
        Neuropharmacology. 1989; 28: 141-147
        • Shimizu K.
        • Stopfer M.
        Gap junctions.
        Curr. Biol. 2013; 23: R1026-R1031
        • Sica D.A.
        Alpha1-adrenergic blockers: current usage considerations.
        J. Clin. Hypertens. (Greenwich). 2005; 7: 757-762
        • Singh C.
        • Rihel J.
        • Prober D.A.
        Neuropeptide Y regulates sleep by modulating noradrenergic signaling.
        Curr. Biol. 2017; 27: 3796-3811
        • Solanes P.
        • Heuze M.L.
        • Maurin M.
        • Bretou M.
        • Lautenschlaeger F.
        • Maiuri P.
        • Terriac E.
        • Thoulouze M.I.
        • Launay P.
        • Piel M.
        • Vargas P.
        • Lennon-Dumenil A.M.
        Space exploration by dendritic cells requires maintenance of myosin II activity by IP3 receptor 1.
        EMBO J. 2015; 34: 798-810
        • Sonohata M.
        • Doi A.
        • Yasaka T.
        • Uta D.
        • Mawatari M.
        • Yoshimura M.
        Noradrenaline modulates mechanically evoked responses in the rat spinal dorsal horn: an in vivo patch-clamp study.
        J. Pain Res. 2019; 12: 1269-1278
        • Spray D.C.
        • White R.L.
        • Mazet F.
        • Bennett M.V.
        Regulation of gap junctional conductance.
        Am. J. Phys. 1985; 248: H753-H764
        • Su C.K.
        Modulation of synchronous sympathetic firing behaviors by endogenous GABAA and glycine receptor-mediated activities in the neonatal rat spinal cord in vitro.
        Neuroscience. 2016; 312: 227-246
        • Su C.-K.
        Rhythmic sympathetic nerve discharges in an in vitro neonatal rat brainstem-spinal cord preparation.
        J. Appl. Physiol. 1999; 87: 1066-1075
        • Su C.K.
        • Chiang C.H.
        • Lee C.M.
        • Fan Y.P.
        • Ho C.M.
        • Shyu L.Y.
        Computational solution of spike overlapping using data-based subtraction algorithms to resolve synchronous sympathetic nerve discharge.
        Front. Comput. Neurosci. 2013; 7: 149
        • Su C.K.
        • Chen Y.Y.
        • Ho C.M.
        Nitric oxide orchestrates a power-law modulation of sympathetic firing behaviors in neonatal rat spinal cords.
        Front. Physiol. 2018; 9: 163
        • Sundaram K.
        • Murugaian J.
        • Sapru H.
        Microinjections of norepinephrine into the intermediolateral cell column of the spinal cord exert excitatory as well as inhibitory effects on the cardiac function.
        Brain Res. 1991; 544: 227-234
        • Takano K.
        • Stanfield P.R.
        • Nakajima S.
        • Nakajima Y.
        Protein kinase C-mediated inhibition of an inward rectifier potassium channel by substance P in nucleus basalis neurons.
        Neuron. 1995; 14: 999-1008
        • Takei K.
        • Shin R.M.
        • Inoue T.
        • Kato K.
        • Mikoshiba K.
        Regulation of nerve growth mediated by inositol 1,4,5-trisphosphate receptors in growth cones.
        Science. 1998; 282: 1705-1708
        • Tatsukawa T.
        • Chimura T.
        • Miyakawa H.
        • Yamaguchi K.
        Involvement of basal protein kinase C and extracellular signal-regulated kinase 1/2 activities in constitutive internalization of AMPA receptors in cerebellar Purkinje cells.
        J. Neurosci. 2006; 26: 4820-4825
        • Zou J.
        • Salarian M.
        • Chen Y.
        • Veenstra R.
        • Louis C.F.
        • Yang J.J.
        Gap junction regulation by calmodulin.
        FEBS Lett. 2014; 588: 1430-1438