PROPERTIES OF A PROTEIN-KINASE C-ACTIVATED CHLORIDE CURRENT IN GUINEA-PIG VENTRICULAR MYOCYTES

被引:46
作者
WALSH, KB
LONG, KJ
机构
[1] Department of Pharmacology, School of Medicine, University of South Carolina, Columbia
关键词
PROTEIN KINASE C; VENTRICULAR MYOCYTES; CL-; CHANNELS; PATCH CLAMP;
D O I
10.1161/01.RES.74.1.121
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Cardiac ventricular myocytes from several species, including the guinea pig, possess a cAMP-dependent protein kinase A (PKA)-activated Cl- channel. In the present study, the properties of a protein kinase C (PKC)-activated Cl- current were studied in isolated guinea pig ventricular myocytes using the whole-cell arrangement of the patch-clamp technique. Intracellular dialysis of ventricular cells with PKC resulted in the activation of a large background current that displayed time-independent kinetics. In the presence of 146 mmol/L external Cl- and 71 mmol/L internal Cl-, the reversal potential (E(rev)) of the background current (-171 +/- 1 mV) was close to that of the Cl- equilibrium potential (-18 mV), and the current versus voltage relation for the current was outward rectifying in shape. When [Cl-](i) or [Cl-](o) was reduced by substitution of Cl- with aspartic acid, E(rev) for the background current shifted in a manner expected for a Cl--selective channel. Based on E(rev) measurements, the permeability sequence for this PKC-activated Cl- channel was determined to be SCN->I->Br(-)similar or equal to Cl-. The PKC-activated Cl- current was not inhibited by the Cl- channel blocker 4,4'-dinitrostilbene-2,2'-disulfonic acid (100 mu mol/L) but could be blocked by anthracene-9-carboxylic acid (1 mmol/L). Activation of the current was abolished in the presence of the PKC inhibitor staurosporine (2.5 mu mol/L). Under conditions designed to cause a maximal activation of the Cl- channels by PKC, the addition of forskolin (1 mu mol/L) to stimulate PKA caused only a slight further increase in the amplitude of the Cl- current. Thus, PKC activates a Cl(-)channel in guinea pig ventricular cells with properties similar but not identical to the PKA-activated channel.
引用
收藏
页码:121 / 129
页数:9
相关论文
共 44 条
  • [1] CHLORIDE CONDUCTANCE REGULATED BY CYCLIC AMP-DEPENDENT PROTEIN-KINASE IN CARDIAC MYOCYTES
    BAHINSKI, A
    NAIRN, AC
    GREENGARD, P
    GADSBY, DC
    [J]. NATURE, 1989, 340 (6236) : 718 - 721
  • [2] DIRECT G-PROTEIN GATING OF ION CHANNELS
    BROWN, AM
    BIRNBAUMER, L
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1988, 254 (03): : H401 - H410
  • [3] BETA-ADRENERGIC INCREASE IN THE CALCIUM CONDUCTANCE OF CARDIAC MYOCYTES STUDIED WITH THE PATCH CLAMP
    BRUM, G
    OSTERRIEDER, W
    TRAUTWEIN, W
    [J]. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1984, 401 (02): : 111 - 118
  • [4] AN AMINO-ACID MUTATION IN A POTASSIUM CHANNEL THAT PREVENTS INHIBITION BY PROTEIN-KINASE-C
    BUSCH, AE
    VARNUM, MD
    NORTH, RA
    ADELMAN, JP
    [J]. SCIENCE, 1992, 255 (5052) : 1705 - 1707
  • [5] CHEMICAL PROBES FOR ANION TRANSPORTERS OF MAMMALIAN-CELL MEMBRANES
    CABANTCHIK, ZI
    GREGER, R
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1992, 262 (04): : C803 - C827
  • [6] CA-2+ CHANNEL MODULATION BY 8-BROMOCYCLIC AMP IN CULTURED HEART-CELLS
    CACHELIN, AB
    DEPEYER, JE
    KOKUBUN, S
    REUTER, H
    [J]. NATURE, 1983, 304 (5925) : 462 - 464
  • [7] PHORBOL ESTER INCREASES CALCIUM CURRENT AND SIMULATES THE EFFECTS OF ANGIOTENSIN-II ON CULTURED NEONATAL RAT-HEART MYOCYTES
    DOSEMECI, A
    DHALLAN, RS
    COHEN, NM
    LEDERER, WJ
    ROGERS, TB
    [J]. CIRCULATION RESEARCH, 1988, 62 (02) : 347 - 357
  • [8] MODULATION OF THE DELAYED RECTIFIER POTASSIUM CURRENT IN FROG CARDIOMYOCYTES BY BETA-ADRENERGIC AGONISTS AND MAGNESIUM
    DUCHATELLEGOURDON, I
    HARTZELL, HC
    LAGRUTTA, AA
    [J]. JOURNAL OF PHYSIOLOGY-LONDON, 1989, 415 : 251 - 274
  • [9] ON THE MECHANISM OF ISOPRENALINE-INDUCED AND FORSKOLIN-INDUCED DEPOLARIZATION OF SINGLE GUINEA-PIG VENTRICULAR MYOCYTES
    EGAN, TM
    NOBLE, D
    NOBLE, SJ
    POWELL, T
    TWIST, VW
    YAMAOKA, K
    [J]. JOURNAL OF PHYSIOLOGY-LONDON, 1988, 400 : 299 - 320
  • [10] FABIATO A, 1988, METHOD ENZYMOL, V157, P378