Skip to main content
The Journal of Physiology logoLink to The Journal of Physiology
. 1995 Aug 15;487(Pt 1):51–56. doi: 10.1113/jphysiol.1995.sp020860

Calcium current reactivation after flash photolysis of nifedipine in skeletal muscle fibres of the frog.

D Feldmeyer 1, P Zöllner 1, B Pohl 1, W Melzer 1
PMCID: PMC1156598  PMID: 7473258

Abstract

1. L-type calcium currents were activated by depolarization of cut muscle fibres of the frog. The current was blocked by the dihydropyridine compound nifedipine (5-10 microM) and reactivated by flash photolysis of the drug. 2. In the presence of nifedipine, increasing the time interval between the onset of depolarization and the flash resulted in progressively faster kinetics of the flash-induced current. This change developed with a slow time course similar to that of normal current activation. 3. A fast gating mode of the normally slow L-type channel was induced by conditioning activation (500 ms prepulses) applied 80 ms before a test step to the same potential. After block by nifedipine, flash-photolysis was carried out 40 ms before the end of the long conditioning pulse. The flash-induced current had the same rapid time course as the current activated by the subsequent test voltage step. 4. Similarly, the time course of current activation was comparable for the voltage-induced fast mode activation (flash applied 5 ms before the test step) and the flash-induced activation 40 ms after the onset of the test depolarization. 5. Our data suggest that in frog skeletal muscle nifedipine inhibits calcium current activation by blocking a rapid channel gating step while the slow conformational change that normally limits the rate of activation of the L-type calcium channel remains unaffected. UV flash illumination results in a fast reactivation indicating that the channels need not be inactivated to be blocked by nifedipine.

Full text

PDF
51

Selected References

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

  1. Bean B. P. Nitrendipine block of cardiac calcium channels: high-affinity binding to the inactivated state. Proc Natl Acad Sci U S A. 1984 Oct;81(20):6388–6392. doi: 10.1073/pnas.81.20.6388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Catterall W. A., Striessnig J. Receptor sites for Ca2+ channel antagonists. Trends Pharmacol Sci. 1992 Jun;13(6):256–262. doi: 10.1016/0165-6147(92)90079-l. [DOI] [PubMed] [Google Scholar]
  3. Feldmeyer D., Melzer W., Pohl B. Effects of gallopamil on calcium release and intramembrane charge movements in frog skeletal muscle fibres. J Physiol. 1990 Feb;421:343–362. doi: 10.1113/jphysiol.1990.sp017948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Feldmeyer D., Melzer W., Pohl B., Zöllner P. Fast gating kinetics of the slow Ca2+ current in cut skeletal muscle fibres of the frog. J Physiol. 1990 Jun;425:347–367. doi: 10.1113/jphysiol.1990.sp018107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Feldmeyer D., Melzer W., Pohl B., Zöllner P. Modulation of calcium current gating in frog skeletal muscle by conditioning depolarization. J Physiol. 1992 Nov;457:639–653. doi: 10.1113/jphysiol.1992.sp019399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Garcia J., Avila-Sakar A. J., Stefani E. Repetitive stimulation increases the activation rate of skeletal muscle Ca2+ currents. Pflugers Arch. 1990 Apr;416(1-2):210–212. doi: 10.1007/BF00370245. [DOI] [PubMed] [Google Scholar]
  7. García J., Tanabe T., Beam K. G. Relationship of calcium transients to calcium currents and charge movements in myotubes expressing skeletal and cardiac dihydropyridine receptors. J Gen Physiol. 1994 Jan;103(1):125–147. doi: 10.1085/jgp.103.1.125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Glossmann H., Striessnig J. Molecular properties of calcium channels. Rev Physiol Biochem Pharmacol. 1990;114:1–105. doi: 10.1007/BFb0031018. [DOI] [PubMed] [Google Scholar]
  9. Gurney A. M., Nerbonne J. M., Lester H. A. Photoinduced removal of nifedipine reveals mechanisms of calcium antagonist action on single heart cells. J Gen Physiol. 1985 Sep;86(3):353–379. doi: 10.1085/jgp.86.3.353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lamb G. D. DHP receptors and excitation-contraction coupling. J Muscle Res Cell Motil. 1992 Aug;13(4):394–405. doi: 10.1007/BF01738035. [DOI] [PubMed] [Google Scholar]
  11. Morad M., Goldman Y. E., Trentham D. R. Rapid photochemical inactivation of Ca2+-antagonists shows that Ca2+ entry directly activates contraction in frog heart. Nature. 1983 Aug 18;304(5927):635–638. doi: 10.1038/304635a0. [DOI] [PubMed] [Google Scholar]
  12. Nakai J., Adams B. A., Imoto K., Beam K. G. Critical roles of the S3 segment and S3-S4 linker of repeat I in activation of L-type calcium channels. Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):1014–1018. doi: 10.1073/pnas.91.3.1014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Nakayama H., Taki M., Striessnig J., Glossmann H., Catterall W. A., Kanaoka Y. Identification of 1,4-dihydropyridine binding regions within the alpha 1 subunit of skeletal muscle Ca2+ channels by photoaffinity labeling with diazipine. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9203–9207. doi: 10.1073/pnas.88.20.9203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Neuhaus R., Rosenthal R., Lüttgau H. C. The effects of dihydropyridine derivatives on force and Ca2+ current in frog skeletal muscle fibres. J Physiol. 1990 Aug;427:187–209. doi: 10.1113/jphysiol.1990.sp018167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Rapp G., Güth K. A low cost high intensity flash device for photolysis experiments. Pflugers Arch. 1988 Feb;411(2):200–203. doi: 10.1007/BF00582315. [DOI] [PubMed] [Google Scholar]
  16. Regulla S., Schneider T., Nastainczyk W., Meyer H. E., Hofmann F. Identification of the site of interaction of the dihydropyridine channel blockers nitrendipine and azidopine with the calcium-channel alpha 1 subunit. EMBO J. 1991 Jan;10(1):45–49. doi: 10.1002/j.1460-2075.1991.tb07919.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Striessnig J., Murphy B. J., Catterall W. A. Dihydropyridine receptor of L-type Ca2+ channels: identification of binding domains for [3H](+)-PN200-110 and [3H]azidopine within the alpha 1 subunit. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10769–10773. doi: 10.1073/pnas.88.23.10769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Tanabe T., Adams B. A., Numa S., Beam K. G. Repeat I of the dihydropyridine receptor is critical in determining calcium channel activation kinetics. Nature. 1991 Aug 29;352(6338):800–803. doi: 10.1038/352800a0. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES