Changes in Cytoplasmic Calcium Induced by Purinergic P2x Receptor Activation in Vascular Smooth Muscle Cells and Sensory Neurons

  • Christopher D. Benham
  • Muriel M. Bouvier
  • Martyn L. Evans
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 304)


It is now widely accepted that ATP is an excitatory sympathetic co-transmitter (reviewed by Burnstock and Kennedy, 1986) which, on release generates fast excitatory junction potentials in arteries (Stjarne, 1986) and some other smooth muscles (Sneddon and Westfall, 1982). These contractile actions of ATP on smooth muscle appear to be due to activation of the P2x subtype of purinoceptor (Burnstock and Kennedy, 1985) which gates a cation permeable channel. In sensory neurons (Krishtal et al., 1983), a very similar ATP receptor/channel also causes depolarization by the activation of inward currents. In vascular smooth muscle, ATP is generally thought to stimulate contraction by activating a mainly sodium permeable conductance that depolarizes the cell (Suzuki, 1985) and opens voltage-gated Ca2+ channels (Burnstock, 1988) allowing calcium entry. The advent of patch-clamp techniques has allowed detailed study of the ATP-activated channels in vascular smooth muscle revealing that the conductance is cation selective (Benham et al., 1987), and that the channels are closely coupled to the ATP receptor (Benham and Tsien, 1987). Results from current reversal potential measurements suggested that the channels are permeable to Ca2+ with a selectivity of three to one over Na+. Bearing in mind the much higher concentration of Na+ present in extracellular saline, the calculated Ca2+ influx is less than 10% of the total ATP activated current. However, permeation calculations are subject to error, especially for Ca2+ permeable channels where the strict conditions of the Goldman equation are not fulfilled (Tsien et al., 1987).


Vascular Smooth Muscle Cell Outward Current Single Smooth Muscle Cell Cation Permeable Channel Excitatory Junction Potential 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Benham, C. D., 1989a, Voltage-gated and agonist mediated rises in intracellular Ca in rat clonal pituitary cells (GH3) held under voltage clamp, J. Physiol, 415: 143.PubMedGoogle Scholar
  2. Benham, C. D., 1989b, ATP-activated channels gate calcium entry in single smooth muscle cells dissociated from rabbit ear artery, J. Physiol., 419: 689.PubMedGoogle Scholar
  3. Benham, C. D. and Bolton, T. B., 1986, Spontaneous transient outward currents in single visceral and vascular smooth muscle cells of rabbit, J. Physiol, 381: 385.PubMedGoogle Scholar
  4. Benham, C. D., Bolton T. B., Byrne N. G., and Large, W. A., 1987, Action of extracellular adenosine triphosphate in single smooth muscle cells dispersed from the rabbit ear artery, J. Physiol., 387: 473.PubMedGoogle Scholar
  5. Benham, C. D., Bolton, T. B., Lang, R. J., and Takewaki, T., 1986, Calcium activated K-channels in single dispersed smooth muscle cells of rabbit jejunum and guinea-pig mesenteric artery, J. Physiol., 371: 45.PubMedGoogle Scholar
  6. Benham, C. D. and Tsien, R. W., 1987, Receptor-operated, Ca-permeable channels activated by ATP in arterial smooth muscle, Nature, 328: 275.PubMedCrossRefGoogle Scholar
  7. Benham, C. D. and Tsien, R. W., 1988, Noradrenaline modulation of calcium channels in single smooth muscle cells from rabbit ear artery, J. Physiol, 404: 767.PubMedGoogle Scholar
  8. Bouvier, M. M., Evans, M. L., Fowler, K., and Benham, C. D., 1990, Calcium influx induced by ATP receptor activation on neurones cultured from rat dorsal root ganglia, J. Physiol., 424: 20P.Google Scholar
  9. Burnstock, G., 1988, Sympathetic purinergic transmission in small blood vessels, Trends Pharmacol Sci., 9: 116.PubMedCrossRefGoogle Scholar
  10. Burnstock, G. and Kennedy, C., 1985, Is there a basis for distinguishing two types of P2-purinoceptor?, Gen. Pharmacol., 16: 433.PubMedCrossRefGoogle Scholar
  11. Burnstock, G. and Kennedy, C., 1986, A dual function for adenosine-5′-triphosphate in the regulation of vascular tone, Circ. Res., 58: 319.PubMedGoogle Scholar
  12. Cobbold, P. and Rink, T. J., 1987, Fluorescence and bioluminescence measurement of cytoplasmic free calcium, Biochem. J., 248: 313.PubMedGoogle Scholar
  13. Forda, S. R. and Kelly, J. S., 1985, The possible modulation of the development of rat dorsal root ganglion neurons by the presence of 5-HT containing neurones of the brainstem in dissociated cell culture, Dev. Brain Res., 22: 55.CrossRefGoogle Scholar
  14. Grynkiewicz, G., Poenie, M., and Tsien, R. Y., 1985, A new generation of Ca indicators with greatly improved fluorescence properties, J. Biol. Chem., 260: 3440.PubMedGoogle Scholar
  15. Hamill, O. P., Marty, A., Neher, E., Sakmann, B., and Sigworth, F. J., 1981, Improved patch-clamp techniques for high resolution current recording from cells and cell free membrane patches, Pflügers Arch., 391: 85.PubMedCrossRefGoogle Scholar
  16. Hernandez-Cruz, A., Sala, F., and Adams, P. R., 1990, Subcellular calcium transients visualised by confocal microscope in a voltage-clamped vertebrate neuron, Science, 247: 858.PubMedCrossRefGoogle Scholar
  17. Jacob, R. and Benham, C. D., 1990, Measuring cytoplasmic calcium in single living cells using fluorescent probes, in: “New Techniques of Optical Microscopy and Microspectrophotometry”, R. J. Cherry, ed., Macmillan Press.Google Scholar
  18. Krishtal, O. A., Marchenko, S. M., and Pidoplichko, V. I., 1983, Receptor for ATP in the membrane of mammalian sensory neurones, Neurosci. Lett., 35: 41.PubMedCrossRefGoogle Scholar
  19. Mayer, M. L. and Westbrook, G. L., 1987, Permeation and block of N-methyl-D-aspartic acid receptor channels by divalent cations in mouse cultured central neurones, J. Physiol, 394: 501.PubMedGoogle Scholar
  20. Sneddon, P., Westfall, D. P., and Fedan, J. S., 1982, Co-transmitters in the motor nerves of the guinea-pig vas deferens: Electrophysiological evidence, Science, 218: 693.PubMedCrossRefGoogle Scholar
  21. Stjarne, L., 1986, New paradigm: Sympathetic transmission by multiple messengers and lateral interaction between monoquantal release sites? Trends Neurosci., 9: 547.CrossRefGoogle Scholar
  22. Suzuki, H., 1985, Electrical responses of smooth muscle cells of the rabbit ear artery to adenosine triphosphate, J. Physiol., 359: 401.PubMedGoogle Scholar
  23. Tsien, R. W., Hess, P., McCleskey, E. W., and Rosenberg, R. L., 1987, Calcium channels: Mechanisms of selectivity, permeation and block, Ann. Rev. Biophys. Biophys. Chem., 16: 265CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Christopher D. Benham
    • 1
  • Muriel M. Bouvier
    • 1
  • Martyn L. Evans
    • 1
  1. 1.SmithKline Beecham PharmaceuticalsThe PinnaclesHarlowEngland

Personalised recommendations