Skip to main content
PMC home page
Biophysical Journal logoLink to Biophysical Journal
. 1998 Oct;75(4):1767–1773. doi: 10.1016/S0006-3495(98)77618-0

Ca2+ removal mechanisms in rat cerebral resistance size arteries.

T Kamishima 1, J G McCarron 1
PMCID: PMC1299848  PMID: 9746518

Abstract

Tissue blood flow and blood pressure are each regulated by the contractile behavior of resistance artery smooth muscle. Vascular diseases such as hypertension have also been attributed to changes in vascular smooth muscle function as a consequence of altered Ca2+ removal. In the present study of Ca2+ removal mechanisms, in dissociated single cells from resistance arteries using fura-2 microfluorimetry and voltage clamp, Ca2+ uptake by the sarcoplasmic reticulum and extrusion by the Ca2+ pump in the cell membrane were demonstrably important in regulating Ca2+. In contrast, the Na+-Ca2+ exchanger played no detectable role in clearing Ca2+. Thus a voltage pulse to 0 mV, from a holding potential of -70 mV, triggered a Ca2+ influx and increased intracellular Ca2+ concentration ([Ca2+]i). On repolarization, [Ca2+]i returned to the resting level. The decline in [Ca2+]i consisted of three phases. Ca2+ removal was fast immediately after repolarization (first phase), then plateaued (second phase), and finally accelerated just before [Ca2+]i returned to resting levels (third phase). Thapsigargin or ryanodine, which each inhibit Ca2+ uptake into stores, did not affect the first but significantly inhibited the third phase. On the other hand, Na+ replacement with choline+ did not affect either the phasic features of Ca2+ removal or the absolute rate of its decline. Ca2+ removal was voltage-independent; holding the membrane potential at 120 mV, rather than at -70 mV, after the voltage pulse to 0 mV, did not attenuate Ca2+ removal rate. These results suggest that Ca2+ pumps in the sarcoplasmic reticulum and the plasma membrane, but not the Na+-Ca2+ exchanger, are important in Ca2+ removal in cerebral resistance artery cells.

Full Text

The Full Text of this article is available as a PDF (123.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aaronson P. I., Benham C. D. Alterations in [Ca2+]i mediated by sodium-calcium exchange in smooth muscle cells isolated from the guinea-pig ureter. J Physiol. 1989 Sep;416:1–18. doi: 10.1113/jphysiol.1989.sp017745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Babcock D. F., Herrington J., Goodwin P. C., Park Y. B., Hille B. Mitochondrial participation in the intracellular Ca2+ network. J Cell Biol. 1997 Feb 24;136(4):833–844. doi: 10.1083/jcb.136.4.833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Balke C. W., Egan T. M., Wier W. G. Processes that remove calcium from the cytoplasm during excitation-contraction coupling in intact rat heart cells. J Physiol. 1994 Feb 1;474(3):447–462. doi: 10.1113/jphysiol.1994.sp020036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bassani R. A., Bassani J. W., Bers D. M. Mitochondrial and sarcolemmal Ca2+ transport reduce [Ca2+]i during caffeine contractures in rabbit cardiac myocytes. J Physiol. 1992;453:591–608. doi: 10.1113/jphysiol.1992.sp019246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Benham C. D., Tsien R. W. A novel receptor-operated Ca2+-permeable channel activated by ATP in smooth muscle. Nature. 1987 Jul 16;328(6127):275–278. doi: 10.1038/328275a0. [DOI] [PubMed] [Google Scholar]
  6. Blaustein M. P., Ashida T., Goldman W. F., Wier W. G., Hamlyn J. M. Sodium/calcium exchange in vascular smooth muscle: a link between sodium metabolism and hypertension. Ann N Y Acad Sci. 1986;488:199–216. doi: 10.1111/j.1749-6632.1986.tb46559.x. [DOI] [PubMed] [Google Scholar]
  7. Drummond R. M., Fay F. S. Mitochondria contribute to Ca2+ removal in smooth muscle cells. Pflugers Arch. 1996 Feb;431(4):473–482. doi: 10.1007/BF02191893. [DOI] [PubMed] [Google Scholar]
  8. Eggermont J. A., Vrolix M., Raeymaekers L., Wuytack F., Casteels R. Ca2+-transport ATPases of vascular smooth muscle. Circ Res. 1988 Feb;62(2):266–278. doi: 10.1161/01.res.62.2.266. [DOI] [PubMed] [Google Scholar]
  9. Fleischmann B. K., Wang Y. X., Pring M., Kotlikoff M. I. Voltage-dependent calcium currents and cytosolic calcium in equine airway myocytes. J Physiol. 1996 Apr 15;492(Pt 2):347–358. doi: 10.1113/jphysiol.1996.sp021313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Friel D. D., Tsien R. W. An FCCP-sensitive Ca2+ store in bullfrog sympathetic neurons and its participation in stimulus-evoked changes in [Ca2+]i. J Neurosci. 1994 Jul;14(7):4007–4024. doi: 10.1523/JNEUROSCI.14-07-04007.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ganitkevich V Y. a., Isenberg G. Depolarization-mediated intracellular calcium transients in isolated smooth muscle cells of guinea-pig urinary bladder. J Physiol. 1991 Apr;435:187–205. doi: 10.1113/jphysiol.1991.sp018505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
  13. Herrington J., Park Y. B., Babcock D. F., Hille B. Dominant role of mitochondria in clearance of large Ca2+ loads from rat adrenal chromaffin cells. Neuron. 1996 Jan;16(1):219–228. doi: 10.1016/s0896-6273(00)80038-0. [DOI] [PubMed] [Google Scholar]
  14. Horowitz A., Menice C. B., Laporte R., Morgan K. G. Mechanisms of smooth muscle contraction. Physiol Rev. 1996 Oct;76(4):967–1003. doi: 10.1152/physrev.1996.76.4.967. [DOI] [PubMed] [Google Scholar]
  15. Kamishima T., McCarron J. G. Depolarization-evoked increases in cytosolic calcium concentration in isolated smooth muscle cells of rat portal vein. J Physiol. 1996 Apr 1;492(Pt 1):61–74. doi: 10.1113/jphysiol.1996.sp021289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kamishima T., McCarron J. G. Regulation of the cytosolic Ca2+ concentration by Ca2+ stores in single smooth muscle cells from rat cerebral arteries. J Physiol. 1997 Jun 15;501(Pt 3):497–508. doi: 10.1111/j.1469-7793.1997.497bm.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kargacin M. E., Kargacin G. J. Direct measurement of Ca2+ uptake and release by the sarcoplasmic reticulum of saponin permeabilized isolated smooth muscle cells. J Gen Physiol. 1995 Sep;106(3):467–484. doi: 10.1085/jgp.106.3.467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. McCarron J. G., Walsh J. V., Jr, Fay F. S. Sodium/calcium exchange regulates cytoplasmic calcium in smooth muscle. Pflugers Arch. 1994 Feb;426(3-4):199–205. doi: 10.1007/BF00374772. [DOI] [PubMed] [Google Scholar]
  19. McGeown J. G., Drummond R. M., McCarron J. G., Fay F. S. The temporal profile of calcium transients in voltage clamped gastric myocytes from Bufo marinus. J Physiol. 1996 Dec 1;497(Pt 2):321–336. doi: 10.1113/jphysiol.1996.sp021771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Poenie M. Alteration of intracellular Fura-2 fluorescence by viscosity: a simple correction. Cell Calcium. 1990 Feb-Mar;11(2-3):85–91. doi: 10.1016/0143-4160(90)90062-y. [DOI] [PubMed] [Google Scholar]
  21. Quayle J. M., Bonev A. D., Brayden J. E., Nelson M. T. Calcitonin gene-related peptide activated ATP-sensitive K+ currents in rabbit arterial smooth muscle via protein kinase A. J Physiol. 1994 Feb 15;475(1):9–13. doi: 10.1113/jphysiol.1994.sp020045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rossier M. F., Python C. P., Burnay M. M., Schlegel W., Vallotton M. B., Capponi A. M. Thapsigargin inhibits voltage-activated calcium channels in adrenal glomerulosa cells. Biochem J. 1993 Dec 1;296(Pt 2):309–312. doi: 10.1042/bj2960309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Shmigol A., Kostyuk P., Verkhratsky A. Dual action of thapsigargin on calcium mobilization in sensory neurons: inhibition of Ca2+ uptake by caffeine-sensitive pools and blockade of plasmalemmal Ca2+ channels. Neuroscience. 1995 Apr;65(4):1109–1118. doi: 10.1016/0306-4522(94)00553-h. [DOI] [PubMed] [Google Scholar]
  24. Smith J. S., Imagawa T., Ma J., Fill M., Campbell K. P., Coronado R. Purified ryanodine receptor from rabbit skeletal muscle is the calcium-release channel of sarcoplasmic reticulum. J Gen Physiol. 1988 Jul;92(1):1–26. doi: 10.1085/jgp.92.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Thastrup O., Cullen P. J., Drøbak B. K., Hanley M. R., Dawson A. P. Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2(+)-ATPase. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2466–2470. doi: 10.1073/pnas.87.7.2466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Vivaudou M. B., Singer J. J., Walsh J. V., Jr Multiple types of Ca2+ channels in visceral smooth muscle cells. Pflugers Arch. 1991 Mar;418(1-2):144–152. doi: 10.1007/BF00370463. [DOI] [PubMed] [Google Scholar]
  27. Wier W. G. Cytoplasmic [Ca2+] in mammalian ventricle: dynamic control by cellular processes. Annu Rev Physiol. 1990;52:467–485. doi: 10.1146/annurev.ph.52.030190.002343. [DOI] [PubMed] [Google Scholar]

Articles from Biophysical Journal are provided here courtesy of The Biophysical Society

RESOURCES