CYCLOPIAZONIC ACID, AN INHIBITOR OF THE SARCOPLASMIC-RETICULUM CA2+-PUMP, REDUCES CA2+-DEPENDENT K+ CURRENTS IN GUINEA-PIG SMOOTH-MUSCLE CELLS

被引:113
作者
SUZUKI, M [1 ]
MURAKI, K [1 ]
IMAIZUMI, Y [1 ]
WATANABE, M [1 ]
机构
[1] NAGOYA CITY UNIV, FAC PHARMACEUT SCI,DEPT CHEM PHARMACOL, 3-1 TANABEDORI,MIZUHO KU, NAGOYA, AICHI 467, JAPAN
关键词
CYCLOPIAZONIC ACID; CA2+-DEPENDENT K+ CURRENT; CA2+-INDUCED CA2+ RELEASE; SARCOPLASMIC RETICULUM; SMOOTH MUSCLE CELLS;
D O I
10.1111/j.1476-5381.1992.tb14475.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 Effects of cyclopiazonic acid (CPA), a specific inhibitor of the Ca2+-ATPase in sarcoplamic reticulum (SR), on membrane ionic currents were examined in single smooth muscle cells freshly isolated from ileal longitudinal strips and urinary bladder of the guinea-pig. 2 Under whole-cell clamp, CPA (1 - 10-mu-M) reduced peak outward current elicited by depolarization in a concentration-dependent manner. The concentration of CPA required for 50% decrease in the peak outward current was approximately 3-mu-M in ileal cells under these conditions. The current reduced by CPA recovered by more than 70% after washout. 3 The transient outward current elicited by application of 5 mm caffeine at a holding potential of - 50 mV in Ca2+ free solution was almost abolished, when the preceding Ca2+-loading of the cell in a solution containing 2.2 mm Ca2+ was performed in the presence of 3-mu-M CPA. 4 When the Ca2+-dependent K+ current (I(K-Ca)) and Ca2+ current (I(Ca)) were inhibited by addition of Ca2+, the remaining delayed rectifier type K+ current was not affected by 10-mu-M CPA. When outward currents were blocked by replacement of K+ by Cs+ in the pipette solution, the remaining I(Ca) was not affected by 10-mu-M CPA. 5 CPA (10-mu-M) did not affect the conductance of single maxi Ca2+-dependent K+ channels or the Cd2+-dependence of their open probability in both inside- and outside-out configurations. 6 These results indicate that I(K-Ca) is selectively and strongly suppressed by CPA. Its effects may be attributed to a decrease in Ca2+-uptake into SR, resulting in a decrease in Ca2+-induced Ca2+ release which is triggered by Ca2+ entering through voltage-dependent Ca2+ channels and therefore less activation of these K channels. 7 CPA may be extremely valuable pharmacological tool for investigating intracellular Ca2+ mobilization and ionic currents regulated by intracellular Ca2+.
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收藏
页码:134 / 140
页数:7
相关论文
共 39 条
[1]   CHARACTERISTICS OF CHLORIDE CURRENTS ACTIVATED BY NORADRENALINE IN RABBIT EAR ARTERY CELLS [J].
AMEDEE, T ;
LARGE, WA ;
WANG, Q .
JOURNAL OF PHYSIOLOGY-LONDON, 1990, 428 :501-516
[2]  
BEHAM CD, 1986, J PHYSL, V281, P385
[3]   CALCIUM-ACTIVATED POTASSIUM CHANNELS IN SINGLE SMOOTH-MUSCLE CELLS OF RABBIT JEJUNUM AND GUINEA-PIG MESENTERIC-ARTERY [J].
BENHAM, CD ;
BOLTON, TB ;
LANG, RJ ;
TAKEWAKI, T .
JOURNAL OF PHYSIOLOGY-LONDON, 1986, 371 :45-67
[4]   ACTION-POTENTIALS AND MEMBRANE CURRENTS OF ISOLATED SINGLE SMOOTH-MUSCLE CELLS OF CAT AND RABBIT COLON [J].
BIELEFELD, DR ;
HUME, JR ;
KRIER, J .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1990, 415 (06) :678-687
[5]   PROPERTIES OF CALCIUM STORES AND TRANSIENT OUTWARD CURRENTS IN SINGLE SMOOTH-MUSCLE CELLS OF RABBIT INTESTINE [J].
BOLTON, TB ;
LIM, SP .
JOURNAL OF PHYSIOLOGY-LONDON, 1989, 409 :385-401
[6]   ACETYLCHOLINE CA2+ STORES REFILLING DIRECTLY INVOLVES A DIHYDROPYRIDINE-SENSITIVE CHANNEL IN DOG TRACHEA [J].
BOURREAU, JP ;
ABELA, AP ;
KWAN, CY ;
DANIEL, EE .
AMERICAN JOURNAL OF PHYSIOLOGY, 1991, 261 (03) :C497-C505
[7]   PARTICIPATION OF CA-2+-ACTIVATED K+ CHANNELS IN ELECTRICAL-ACTIVITY OF CANINE GASTRIC SMOOTH-MUSCLE [J].
CARL, A ;
MCHALE, NG ;
PUBLICOVER, NG ;
SANDERS, KM .
JOURNAL OF PHYSIOLOGY-LONDON, 1990, 429 :205-221
[8]   CHARACTERIZATION OF MACROSCOPIC OUTWARD CURRENTS OF CANINE COLONIC MYOCYTES [J].
COLE, WC ;
SANDERS, KM .
AMERICAN JOURNAL OF PHYSIOLOGY, 1989, 257 (03) :C461-C469
[9]   MUSCARINIC SUPPRESSION OF CA-2+-DEPENDENT K-CURRENT IN COLONIC SMOOTH-MUSCLE [J].
COLE, WC ;
CARL, A ;
SANDERS, KM .
AMERICAN JOURNAL OF PHYSIOLOGY, 1989, 257 (03) :C481-C487
[10]  
DENG HW, 1991, ACTA PHARM SINIC, V12, P53