|
|
||||||||
1 Institut National de la Santé et de la Recherche Médicale, Unité 460, Faculté de Médecine Xavier Bichat, Paris; and 2 Service de Chirurgie Cardiaque, Hôpital Xavier Bichat, 75018 Paris, France
The effects of tyrosine protein kinases
(TK) on the L-type Ca2+ current (ICa)
were examined in whole cell patch-clamped human atrial myocytes. The TK
inhibitors genistein (50 µM), lavendustin A (50 µM), and tyrphostin
23 (50 µM) stimulated ICa by 132 ± 18% (P < 0.001), 116 ± 18% (P < 0.05), and 60 ± 6% (P < 0.001), respectively. After ICa
stimulation by genistein, external application of isoproterenol (1 µM) caused an additional increase in ICa.
Dialyzing the cells with a protein kinase A inhibitor suppressed the
effect of isoproterenol on ICa but not that of
genistein. Inhibition of protein kinase C (PKC) by pretreatment of
cells with 100 nM staurosporine or 100 nM calphostin C prevented the
effects of genistein on ICa. The PKC activator
phorbol 12-myristate 13-acetate (PMA), after an initial stimulation (75 ± 17%, P < 0.05), decreased ICa
(
36 ± 5%, P < 0.001). Once the inhibitory effect of
PMA on ICa had stabilized, genistein strongly
stimulated the current (323 ± 25%, P < 0.05). Pretreating
myocytes with genistein reduced the inhibitory effect of PMA on
ICa. We conclude that, in human atrial myocytes, TK
inhibit ICa via a mechanism that involves PKC.
human cardiac cells; whole cell patch clamp; L-type calcium channels; tyrosine kinase inhibitors
This article has been cited by other articles:
![]() |
S.-S. Zhou, L.-B. Zhang, W.-P. Sun, F.-C. Xiao, Y.-M. Zhou, Y.-J. Li, and D.-L. Li Heart/Cardiac Muscle: Effects of monocarboxylic acid-derived Cl- channel blockers on depolarization-activated potassium currents in rat ventricular myocytes Exp Physiol, May 1, 2007; 92(3): 549 - 559. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. A.G. van der Heyden, T. J.M. Wijnhoven, and T. Opthof Molecular aspects of adrenergic modulation of cardiac L-type Ca2+ channels Cardiovasc Res, January 1, 2005; 65(1): 28 - 39. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. M. Tipparaju, R. Kumar, Y. Wang, R. W. Joyner, and M. B. Wagner Developmental differences in L-type calcium current of human atrial myocytes Am J Physiol Heart Circ Physiol, May 1, 2004; 286(5): H1963 - H1969. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. W. Carter and N. L. Kanagy Mechanism of enhanced calcium sensitivity and alpha 2-AR vasoreactivity in chronic NOS inhibition hypertension Am J Physiol Heart Circ Physiol, January 1, 2003; 284(1): H309 - H316. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. D. Keef, J. R. Hume, and J. Zhong Regulation of cardiac and smooth muscle Ca2+ channels (CaV1.2a,b) by protein kinases Am J Physiol Cell Physiol, December 1, 2001; 281(6): C1743 - C1756. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. J. Davis, X. Wu, T. R. Nurkiewicz, J. Kawasaki, P. Gui, M. A. Hill, and E. Wilson Regulation of ion channels by protein tyrosine phosphorylation Am J Physiol Heart Circ Physiol, November 1, 2001; 281(5): H1835 - H1862. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Boixel, S. Dinanian, L. Lang-Lazdunski, J.-J. Mercadier, and S. N. Hatem Characterization of effects of endothelin-1 on the L-type Ca2+ current in human atrial myocytes Am J Physiol Heart Circ Physiol, August 1, 2001; 281(2): H764 - H773. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. J. Kamp and J. W. Hell Regulation of Cardiac L-Type Calcium Channels by Protein Kinase A and Protein Kinase C Circ. Res., December 8, 2000; 87(12): 1095 - 1102. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. J. Alden, P. H. Goldspink, S. W. Ruch, P. M. Buttrick, and J. Garcia Enhancement of L-type Ca2+ current from neonatal mouse ventricular myocytes by constitutively active PKC-beta II Am J Physiol Cell Physiol, April 1, 2002; 282(4): C768 - C774. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Boixel, W. Gonzalez, L. Louedec, and S. N. Hatem Mechanisms of L-Type Ca2+ Current Downregulation in Rat Atrial Myocytes During Heart Failure Circ. Res., September 28, 2001; 89(7): 607 - 613. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |