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. 1990 Apr 1;95(4):679–696. doi: 10.1085/jgp.95.4.679

Blockade of current through single calcium channels by trivalent lanthanide cations. Effect of ionic radius on the rates of ion entry and exit

PMCID: PMC2216337  PMID: 2159974

Abstract

Currents flowing through single dihydropyridine-sensitive Ca2+ channels were recorded from cell-attached patches on C2 myotubes. In the presence of dihydropyridine agonist to prolong the duration of single- channel openings, adding micromolar concentrations of lanthanum (La), cerium (Ce), neodymium (Nd), gadolinium (Gd), dysprosium (Dy), or ytterbium (Yb) to patch electrodes containing 110 mM BaCl2 caused the unitary Ba2+ currents to fluctuate between fully open and shut states. The kinetics of channel blockade followed the predictions of a simple open channel block model in which the fluctuations of the single- channel current arose from the entry and exit of blocking ions from the pore. Entry rates for all the lanthanides tested were relatively insensitive to membrane potential, however, exit rates depended strongly on membrane potential increasing approximately e-fold per 23 mV with hyperpolarization. Individual lanthanide ions differed in both the absolute rates of ion entry and exit: entry rates decreased as cationic radius decreased; exit rates also decreased with cationic radius during the first part of the lanthanide series but then showed little change during the latter part of the series. Overall, the results support the idea that smaller ions enter the channel more slowly, presumably because they dehydrate more slowly; smaller ions also bind more tightly to a site within the channel pore, but lanthanide residence time within the channel approaches a maximum for the smaller cations with radii less than or equal to that of Ca2+.

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Selected References

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  1. Almers W., McCleskey E. W. Non-selective conductance in calcium channels of frog muscle: calcium selectivity in a single-file pore. J Physiol. 1984 Aug;353:585–608. doi: 10.1113/jphysiol.1984.sp015352. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alnaes E., Rahamimoff R. Dual action of praseodymium (Pr3+) on transmitter release at the frog neuromuscular synapse. Nature. 1974 Feb 15;247(5441):478–479. doi: 10.1038/247478a0. [DOI] [PubMed] [Google Scholar]
  3. Armstrong C. M. Inactivation of the potassium conductance and related phenomena caused by quaternary ammonium ion injection in squid axons. J Gen Physiol. 1969 Nov;54(5):553–575. doi: 10.1085/jgp.54.5.553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Armstrong C. M. Time course of TEA(+)-induced anomalous rectification in squid giant axons. J Gen Physiol. 1966 Nov;50(2):491–503. doi: 10.1085/jgp.50.2.491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Byerly L., Chase P. B., Stimers J. R. Permeation and interaction of divalent cations in calcium channels of snail neurons. J Gen Physiol. 1985 Apr;85(4):491–518. doi: 10.1085/jgp.85.4.491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Curtis M. J., Quastel D. M., Saint D. A. Lanthanum as a surrogate for calcium in transmitter release at mouse motor nerve terminals. J Physiol. 1986 Apr;373:243–260. doi: 10.1113/jphysiol.1986.sp016045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fukushima Y. Blocking kinetics of the anomalous potassium rectifier of tunicate egg studied by single channel recording. J Physiol. 1982 Oct;331:311–331. doi: 10.1113/jphysiol.1982.sp014374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fukushima Y., Hagiwara S. Currents carried by monovalent cations through calcium channels in mouse neoplastic B lymphocytes. J Physiol. 1985 Jan;358:255–284. doi: 10.1113/jphysiol.1985.sp015550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hagiwara S., Byerly L. Calcium channel. Annu Rev Neurosci. 1981;4:69–125. doi: 10.1146/annurev.ne.04.030181.000441. [DOI] [PubMed] [Google Scholar]
  10. Hagiwara S. Ca-dependent action potential. Membranes. 1975;3:359–381. [PubMed] [Google Scholar]
  11. Hagiwara S., Takahashi K. Surface density of calcium ions and calcium spikes in the barnacle muscle fiber membrane. J Gen Physiol. 1967 Jan;50(3):583–601. doi: 10.1085/jgp.50.3.583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hague D. N. Dynamics of substitution at metal ions. Mol Biol Biochem Biophys. 1977;24:84–106. doi: 10.1007/978-3-642-81117-3_3. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Hess P., Lansman J. B., Tsien R. W. Calcium channel selectivity for divalent and monovalent cations. Voltage and concentration dependence of single channel current in ventricular heart cells. J Gen Physiol. 1986 Sep;88(3):293–319. doi: 10.1085/jgp.88.3.293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hess P., Lansman J. B., Tsien R. W. Different modes of Ca channel gating behaviour favoured by dihydropyridine Ca agonists and antagonists. Nature. 1984 Oct 11;311(5986):538–544. doi: 10.1038/311538a0. [DOI] [PubMed] [Google Scholar]
  16. Hess P., Tsien R. W. Mechanism of ion permeation through calcium channels. 1984 May 31-Jun 6Nature. 309(5967):453–456. doi: 10.1038/309453a0. [DOI] [PubMed] [Google Scholar]
  17. Hoshi T., Smith S. J. Large depolarization induces long openings of voltage-dependent calcium channels in adrenal chromaffin cells. J Neurosci. 1987 Feb;7(2):571–580. doi: 10.1523/JNEUROSCI.07-02-00571.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Inestrosa N. C., Miller J. B., Silberstein L., Ziskind-Conhaim L., Hall Z. W. Developmental regulation of 16S acetylcholinesterase and acetylcholine receptors in a mouse muscle cell line. Exp Cell Res. 1983 Sep;147(2):393–405. doi: 10.1016/0014-4827(83)90221-5. [DOI] [PubMed] [Google Scholar]
  19. Lansman J. B., Hess P., Tsien R. W. Blockade of current through single calcium channels by Cd2+, Mg2+, and Ca2+. Voltage and concentration dependence of calcium entry into the pore. J Gen Physiol. 1986 Sep;88(3):321–347. doi: 10.1085/jgp.88.3.321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Linkhart T. A., Clegg C. H., Hauschika S. D. Myogenic differentiation in permanent clonal mouse myoblast cell lines: regulation by macromolecular growth factors in the culture medium. Dev Biol. 1981 Aug;86(1):19–30. doi: 10.1016/0012-1606(81)90311-0. [DOI] [PubMed] [Google Scholar]
  21. Martin R. B., Richardson F. S. Lanthanides as probes for calcium in biological systems. Q Rev Biophys. 1979 May;12(2):181–209. doi: 10.1017/s0033583500002754. [DOI] [PubMed] [Google Scholar]
  22. Mayer C. J., van Breemen C., Casteels T. The action of lanthanum and D600 on the calcium exchange in the smooth muscle cells of the guinea-pig Taenia coli. Pflugers Arch. 1972;337(4):333–350. doi: 10.1007/BF00586650. [DOI] [PubMed] [Google Scholar]
  23. Miledi R. Lanthanum ions abolish the "calcium response" of nerve terminals. Nature. 1971 Feb 5;229(5284):410–411. doi: 10.1038/229410a0. [DOI] [PubMed] [Google Scholar]
  24. Mines G. R. The action of beryllium, lanthanum, yttrium and cerium on the frog's heart. J Physiol. 1910 May 13;40(4):327–346. doi: 10.1113/jphysiol.1910.sp001373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Nachshen D. A. Selectivity of the Ca binding site in synaptosome Ca channels. Inhibition of Ca influx by multivalent metal cations. J Gen Physiol. 1984 Jun;83(6):941–967. doi: 10.1085/jgp.83.6.941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Neher E., Steinbach J. H. Local anaesthetics transiently block currents through single acetylcholine-receptor channels. J Physiol. 1978 Apr;277:153–176. doi: 10.1113/jphysiol.1978.sp012267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sanborn W. G., Langer G. A. Specific uncoupling of excitation and contraction in mammalian cardiac tissue by lanthanum. J Gen Physiol. 1970 Aug;56(2):191–217. doi: 10.1085/jgp.56.2.191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Triggle C. R., Triggle D. J. An analysis of the action of cations of the lanthanide series on the mechanical responses of guinea-pig ileal longitudinal muscle. J Physiol. 1976 Jan;254(1):39–54. doi: 10.1113/jphysiol.1976.sp011219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Woodhull A. M. Ionic blockage of sodium channels in nerve. J Gen Physiol. 1973 Jun;61(6):687–708. doi: 10.1085/jgp.61.6.687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Yaffe D., Saxel O. Serial passaging and differentiation of myogenic cells isolated from dystrophic mouse muscle. Nature. 1977 Dec 22;270(5639):725–727. doi: 10.1038/270725a0. [DOI] [PubMed] [Google Scholar]

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