Tyrosine kinase and protein kinase C regulate L-type Ca2+ current cooperatively in human atrial myocytes

被引:41
作者
Boixel, C
Tessier, S
Pansard, Y
Lang-Lazdunski, L
Mercadier, JJ
Hatem, SN
机构
[1] Fac Med Xavier Bichat, INSERM U460, F-75018 Paris, France
[2] Hop Xavier Bichat, Serv Chirurg Cardiaque, F-75018 Paris, France
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2000年 / 278卷 / 02期
关键词
human cardiac cells; whole cell patch clamp; L-type calcium channels; tyrosine kinase inhibitors;
D O I
10.1152/ajpheart.2000.278.2.H670
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The effects of tyrosine protein kinases (TK) on the L-type Ca2+ current (I-Ca) were examined in whole cell patch-clamped human atrial myocytes. The TK inhibitors genistein (50 mu M), lavendustin A (50 mu M), and tyrphostin 23 (50 mu M) stimulated I-Ca by 132 +/- 18% (P < 0.001), 116 +/- 18% (P < 0.05), and 60 +/- 6% (P < 0.001), respectively. After I-Ca stimulation by genistein, external application of isoproterenol(1 mu M) caused an additional increase in I-Ca. Dialyzing the cells with a protein kinase A inhibitor suppressed the effect of isoproterenol on I-Ca 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 I-Ca. The PKC activator phorbol 12-myristate 13-acetate (PMA), after an initial stimulation (75 +/- 17%, Pt 0.05), decreased I-Ca (-36 +/- 5%, P < 0.001). Once the inhibitory effect of PMA on I-Ca had stabilized, genistein strongly stimulated the current (323 +/- 25%, P < 0.05) Pretreating myocytes with genistein reduced the inhibitory effect of PMA on I-Ca. We conclude that, in human atrial myocytes, TK inhibit I-Ca via a mechanism that involves PKC.
引用
收藏
页码:H670 / H676
页数:7
相关论文
共 26 条
[11]   NITRIC-OXIDE REGULATES THE CALCIUM CURRENT IN ISOLATED HUMAN ATRIAL MYOCYTES [J].
KIRSTEIN, M ;
RIVETBASTIDE, M ;
HATEM, S ;
BENARDEAU, A ;
MERCADIER, JJ ;
FISCHMEISTER, R .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 95 (02) :794-802
[12]  
LEGRAND B, 1994, CARDIOVASC RES, V28, P548
[13]   PROTEIN-TYROSINE KINASE PYK2 INVOLVED IN CA2+-INDUCED REGULATION OF ION-CHANNEL AND MAP KINASE FUNCTIONS [J].
LEV, S ;
MORENO, H ;
MARTINEZ, R ;
CANOLL, P ;
PELES, E ;
MUSACCHIO, JM ;
PLOWMAN, GD ;
RUDY, B ;
SCHLESSINGER, J .
NATURE, 1995, 376 (6543) :737-745
[14]   TYROSINE KINASE INHIBITION - AN APPROACH TO DRUG DEVELOPMENT [J].
LEVITZKI, A ;
GAZIT, A .
SCIENCE, 1995, 267 (5205) :1782-1788
[15]   DECREASED PHOSPHORYLATION OF 4 20-KDA PROTEINS PRECEDES STAUROSPORINE-INDUCED DISRUPTION OF THE ACTIN/MYOSIN CYTOSKELETON IN RAT ASTROCYTES [J].
MOBLEY, PL ;
HEDBERG, K ;
BONIN, L ;
CHEN, BY ;
GRIFFITH, OH .
EXPERIMENTAL CELL RESEARCH, 1994, 214 (01) :55-66
[16]   PROTECTION OF HUMAN LEFT-VENTRICULAR MYOCARDIUM FROM CUTTING INJURY WITH 2,3-BUTANEDIONE MONOXIME [J].
MULIERI, LA ;
HASENFUSS, G ;
ITTLEMAN, F ;
BLANCHARD, EM ;
ALPERT, NR .
CIRCULATION RESEARCH, 1989, 65 (05) :1441-1444
[17]  
OUADID H, 1992, MOL PHARMACOL, V41, P346
[18]   Tyrphostin 23 blocks phosphorylation of p42 but not p38 mitogen-activated protein kinase by zooxanthellatoxin-A [J].
Rho, MC ;
Nakahata, N ;
Nakamura, H ;
Murai, A ;
Ohizumi, Y .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1997, 319 (2-3) :375-378
[19]   cGMP-stimulated cyclic nucleotide phosphodiesterase regulates the basal calcium current in human atrial myocytes [J].
RivetBastide, M ;
Vandecasteele, G ;
Hatem, S ;
Verde, I ;
Benardeau, A ;
Mercadier, JJ ;
Fischmeister, R .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 99 (11) :2710-2718
[20]   Calcium- and protein kinase C-dependent activation of the tyrosine kinase PYK2 by angiotensin II in vascular smooth muscle [J].
Sabri, A ;
Govindarajan, G ;
Griffin, TM ;
Byron, KL ;
Samarel, AM ;
Lucchesi, PA .
CIRCULATION RESEARCH, 1998, 83 (08) :841-851