Skip to main content
Log in

Modulation of Ca-channel current by an adenosine analog mediated by a GTP-binding protein in chick sensory neurons

  • Excitable Tissues and Central Nervous Physiology
  • Published:
Pflügers Archiv Aims and scope Submit manuscript

Abstract

Inhibitory modulation of the high-voltage-activated (HVA) Ca-channel current by 2-chloroadenosine (2CA) was studied in chick sensory neurons using the whole-cell clamp method. 2CA reduced the ωCTX-sensitive HVA-current (Aosaki and Kasai 1989) in a dose-dependent manner with aK d of 0.8 μM. The inhibition by 2CA was also voltage-dependent, being maximal at hyperpolarized potentials, and completely removed at potentials more positive than 30 mV. This voltage-dependence of 2CA action was also evident as a progressive increase in Ca-channel current magnitude during a depolarization which could be described by a single exponential function and which became faster at larger depolarizations. The concentration of 2CA affected the steady-state reduction in Ca-channel current, but did not alter the time-course of current increase during depolarization. The voltage-dependent effect of 2CA was mimicked by intracellular application of GTP-γS, but not by phorbol ester, arachidonic acid or nitroprusside. These results are consistent with model in which 2CA activates a G-protein, which then unmasks an additional activation gate on the Ca-channel.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

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

    Google Scholar 

  • Castagna M, Takai Y, Kaibuchi K, Sano K, Kikkawa U, Nishizuka Y (1982) Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem 257:7847–7851

    Google Scholar 

  • Dolphin AC, Scott RH (1987) Calcium channel currents and their inhibition by (−)-baclofen in rat sensory neurones: modulation by guanosine nucleotides. J Physiol (Lond) 386:1–17

    Google Scholar 

  • Dunlap K, Fischbach GD (1978) Neurotransmitters decrease the calcium component of sensory neurone action potentials. Nature 276:837–839

    Google Scholar 

  • Dunlap K, Fischbach GD (1981) Neurotransmitters decrease the calcium conductance activated by depolarization of embryonic sensory neurones. J Physiol (Lond) 317:519–535

    Google Scholar 

  • Forscher P, Oxford GS, Shultz D (1986) Noradrenaline modulates calcium channels in avian dorsal root ganglion cells through tight receptor-channel coupling. J Physiol (Lond) 379:131–144

    Google Scholar 

  • Gross RA, Macdonald RL (1987) Dynorphin A selectively reduces a large transient (N-type) calcium current of mouse dorsal root ganglion neurones in cell culture. Proc Natl Acad Sci USA 84:5469–5473

    Google Scholar 

  • Hescheler J, Rosenthal W, Trautwein W, Shultz G (1987) The GTP-binding protein, Go, regulates neuronal calcium channels. Nature 325:445–447

    Google Scholar 

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

    Google Scholar 

  • Kaibuchi K, Takai Y, Sawamura M, Hoshijima M, Fujikura T, Nishizuka Y (1983) Synergistic functions of protein phosphorylation and calcium mobilization in platelet activation. J Biol Chem 258:6701–6704

    Google Scholar 

  • Kasai H, Aosaki T (1988) Divalent cation-dependent inactivation of the high-voltage-activated Ca channel current in chick sensory neurons. Pflügers Arch 411:695–697

    Google Scholar 

  • Macdonald RL, Werz MA (1986) Dynorphin A decreases voltagedependent calcium conductance of mouse dorsal root ganglion neurones. J Physiol 377:237–249

    Google Scholar 

  • Macdonald RL, Skerritt JH, Werz MA (1986) Adenosine agonists reduce voltage-dependent calcium conductance of mouse sensory neurons in cell culture. J Physiol 370:75–90

    Google Scholar 

  • Madison DV, Fox AP, Tsien RW (1987) Adenosine reduces an inactivating component of calcium current in hippocampal CA3 neurons. Biophys J 51:30a

    Google Scholar 

  • Marchetti C, Carbone E, Lux HD (1986) Effects of dopamine and noradrenaline on Ca channels of cultured sensory and sympathetic neurons of chick. Pflügers Arch 406:104–111

    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 83:184–188

    Google Scholar 

  • Tsunoo A, Yoshii M, Narahashi T (1986) Block of calcium channels by enkephalin and somatostatin in neuroblastoma-glioma hybrid NG 108-15 cells. Proc Natl Acad Sci USA 83:9832–9836

    Google Scholar 

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

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kasai, H., Aosaki, T. Modulation of Ca-channel current by an adenosine analog mediated by a GTP-binding protein in chick sensory neurons. Pflugers Arch. 414, 145–149 (1989). https://doi.org/10.1007/BF00580956

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00580956

Key words

Navigation