A NOVEL MONOVALENT CATION CHANNEL ACTIVATED BY INOSITOL TRISPHOSPHATE IN THE PLASMA-MEMBRANE OF RAT MEGAKARYOCYTES

被引:29
作者
SOMASUNDARAM, B
MAHAUTSMITH, MP
机构
[1] Physiological Laboratory, Cambridge, CB2 3EG, Downing Street
关键词
D O I
10.1074/jbc.270.28.16638
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The activation of a monovalent cation current was studied in rat megakaryocytes using patch clamp techniques combined with photometric measurements of intracellular concentrations of Ca2+ ([Ca2+](i)) and Na+. ADP evoked a release of [Ca2+](i) and transiently activated a monovalent cation-selective channel, which, at negative potentials and under physiological conditions, would be expected to carry an inward Na+ current. The single channel conductance, estimated by noise analysis from whole cell currents at -50 to -60 mV was 9 picosiemens. Thapsigargin induced [Ca2+](i) increases failed to stimulate the monovalent cation current, suggesting that neither [Ca2+](i) nor the depletion of internal Ca2+ stores were activators of this conductance. However, buffering of [Ca2+](i) changes with 1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid showed that both activation and inactivation of the current were accelerated by a rise in [Ca2+](i). The monovalent cation conductance was activated by internal perfusion with inositol 1,4,5-trisphosphate, both in the presence and in the absence of a rise in [Ca2+](i). Internal perfusion with inositol 2,4,5-trisphosphate, the poorly metabolizable isomer of inositol trisphosphate, similarly activated the monovalent cation current, whereas 1,3,4,5-tetrakisphosphate neither activated a current nor modified the ADP-induced monovalent current. Heparin, added to the pipette, blocked activation of the channel by ADP. The intracellular concentration of Na+, monitored by sodium-binding benzofuran isopthalate, increased by 10-20 mM in response to ADP under pseudophysiological conditions. We conclude the existence of a novel nonselective cation channel in the plasma membrane of rat megakaryocytes, which is activated by IP3 and can lead to increases in cytosolic Na+ after stimulation by ADP.
引用
收藏
页码:16638 / 16644
页数:7
相关论文
共 42 条
[31]   INOSITOL 1,4,5-TRISPHOSPHATE-INDUCED CALCIUM RELEASE FROM PLATELET PLASMA-MEMBRANE VESICLES [J].
RENGASAMY, A ;
FEINBERG, H .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1988, 150 (03) :1021-1026
[32]   ODOR STIMULI TRIGGER INFLUX OF CALCIUM INTO OLFACTORY NEURONS OF THE CHANNEL CATFISH [J].
RESTREPO, D ;
MIYAMOTO, T ;
BRYANT, BP ;
TEETER, JH .
SCIENCE, 1990, 249 (4973) :1166-1168
[33]   CALCIUM SIGNALING IN HUMAN PLATELETS [J].
RINK, TJ ;
SAGE, SO .
ANNUAL REVIEW OF PHYSIOLOGY, 1990, 52 :431-449
[34]   RESTING AND ADP-EVOKED CHANGES IN CYTOSOLIC FREE SODIUM CONCENTRATION IN HUMAN PLATELETS LOADED WITH THE INDICATOR SBFI [J].
SAGE, SO ;
RINK, TJ ;
MAHAUTSMITH, MP .
JOURNAL OF PHYSIOLOGY-LONDON, 1991, 441 :559-573
[35]   THE VARIANCE OF SODIUM CURRENT FLUCTUATIONS AT THE NODE OF RANVIER [J].
SIGWORTH, FJ .
JOURNAL OF PHYSIOLOGY-LONDON, 1980, 307 (OCT) :97-129
[36]   3 CATION INFLUX CURRENTS ACTIVATED BY PURINERGIC RECEPTOR STIMULATION IN RAT MEGAKARYOCYTES [J].
SOMASUNDARAM, B ;
MAHAUTSMITH, MP .
JOURNAL OF PHYSIOLOGY-LONDON, 1994, 480 :225-231
[37]  
STENGL M, 1994, J COMP PHYSIOL A, V174, P187
[38]  
SUPATTAPONE S, 1988, J BIOL CHEM, V263, P1530
[39]   THAPSIGARGIN, A NOVEL MOLECULAR PROBE FOR STUDYING INTRACELLULAR CALCIUM RELEASE AND STORAGE [J].
THASTRUP, O ;
DAWSON, AP ;
SCHARFF, O ;
FODER, B ;
CULLEN, PJ ;
DROBAK, BK ;
BJERRUM, PJ ;
CHRISTENSEN, SB ;
HANLEY, MR .
AGENTS AND ACTIONS, 1989, 27 (1-2) :17-23
[40]   CYTOPLASMIC CA2+ OSCILLATION IN RAT MEGAKARYOCYTES EVOKED BY A NOVEL TYPE OF PURINOCEPTOR [J].
UNEYAMA, C ;
UNEYAMA, H ;
AKAIKE, N .
JOURNAL OF PHYSIOLOGY-LONDON, 1993, 470 :731-749