2 DISTINCT MODES OF CA2+ SIGNALING BY ACH IN RAT PANCREATIC BETA-CELLS - CONCENTRATION, GLUCOSE DEPENDENCE AND CA2+ ORIGIN

被引:35
作者
YADA, T
HAMAKAWA, N
YAEKURA, K
机构
[1] Department of Physiology, Kagoshima University School of Medicine
来源
JOURNAL OF PHYSIOLOGY-LONDON | 1995年 / 488卷 / 01期
关键词
D O I
10.1113/jphysiol.1995.sp020942
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
1. Calcium signalling by acetylcholine (ACh) in single rat pancreatic beta-cells was studied. The cytosolic free Ca2+ concentration ([Ca2+](i)) was measured) by dual-wavelength fura-2 microfluorometry. 2. In the presence of basal glucose (2.8 mM), 10(-6) to 10(-4)M ACh (high ACh) transiently increased [Ca2+](i). The [Ca2+](i) response to 10(-5) M ACh was little altered under Ca2+-free conditions. Brief pulses of 10(-5) M ACh evoked successive [Ca2+](i) responses, which were progressively inhibited by 0.2-0.5 mu M thapsigargin, a specific inhibitor of the endoplasmic reticulum (ER) Ca2+ pump. 3. Elevation of glucose to 8.3 mM, a concentration which stimulates insulin release, increased [Ca2+](i) to an initial peak followed by a sustained, moderate elevation. Addition of 10(-8) to 10(-7) M ACh (low ACh) evoked a further increase in [Ca2+](i). The [C2+](i) response to 10(-7) M ACh was completely inhibited under Ca2+-free conditions by 1 mu M nitrendipine, a blocker of L-type Ca2+ channels, and by 100 mu M diazoxide, an opener of ATP-sensitive K+ channels. 4. In the presence of 8.3 mM glucose, [Ca2+], responses to 10(-5) nr ACh were reduced but not abolished by Ca2+-free conditions, nitrendipine and diazoxide. Successive [Ca2+](i) transients induced by 10(-5) M ACh pulses in the presence of nitrendipine were progressively inhibited by thapsigargin. 5. The results revealed two distinct modes of Ca2+ signalling: low ACh increases [Ca2+](i) by stimulating Ca2+ influx through voltage-dependent L-type Ca2+ channels only in the p-cells in which glucose has already elevated [Ca2+](i), while high ACh increases [Ca2+](i) at basal as well as stimulatory glucose concentrations by releasing Ca2+ from the ER. The former mechanism is likely to relate to the potentiator action and the latter to the initiator action of ACh on insulin release. High ACh and elevated glucose provoke both modes of Ca2+ signalling.
引用
收藏
页码:13 / 24
页数:12
相关论文
共 41 条
[1]   NEUROPEPTIDERGIC VERSUS CHOLINERGIC AND ADRENERGIC REGULATION OF ISLET HORMONE-SECRETION [J].
AHREN, B ;
TABORSKY, GJ ;
PORTE, D .
DIABETOLOGIA, 1986, 29 (12) :827-836
[2]   EXOCYTOSIS ELICITED BY ACTION-POTENTIALS AND VOLTAGE-CLAMP CALCIUM CURRENTS IN INDIVIDUAL MOUSE PANCREATIC B-CELLS [J].
AMMALA, C ;
ELIASSON, L ;
BOKVIST, K ;
LARSSON, O ;
ASHCROFT, FM ;
RORSMAN, P .
JOURNAL OF PHYSIOLOGY-LONDON, 1993, 472 :665-688
[3]   DIRECT ENHANCEMENT OF INSULIN-SECRETION BY VAGAL STIMULATION OF ISOLATED PANCREAS [J].
BERGMAN, RN ;
MILLER, RE .
AMERICAN JOURNAL OF PHYSIOLOGY, 1973, 225 (02) :481-486
[4]   MECHANISMS OF ACTIVATED CA2+ ENTRY IN THE RAT PANCREATOMA CELL-LINE, AR4-2J [J].
BIRD, GS ;
TAKEMURA, H ;
THASTRUP, O ;
PUTNEY, JW ;
MENNITI, FS .
CELL CALCIUM, 1992, 13 (01) :49-58
[5]  
BLONDEL O, 1993, J BIOL CHEM, V268, P11356
[6]   GLUCOSE AND ACETYLCHOLINE HAVE DIFFERENT EFFECTS ON THE PLATEAU PACEMAKER OF PANCREATIC-ISLET CELLS [J].
COOK, DL ;
CRILL, WE ;
PORTE, D .
DIABETES, 1981, 30 (07) :558-561
[7]   INSULIN RELEASE, CGMP, CAMP, AND MEMBRANE-POTENTIAL IN ACETYLCHOLINE-STIMULATED ISLETS [J].
GAGERMAN, E ;
IDAHL, LA ;
MEISSNER, HP ;
TALJEDAL, IB .
AMERICAN JOURNAL OF PHYSIOLOGY, 1978, 235 (05) :E493-E500
[8]   THE ROLE OF PROTEIN-KINASE-C IN SIGNAL-TRANSDUCTION THROUGH VASOPRESSIN AND ACETYLCHOLINE-RECEPTORS IN PANCREATIC B-CELLS FROM NORMAL MOUSE [J].
GAO, ZY ;
GILON, P ;
HENQUIN, JC .
ENDOCRINOLOGY, 1994, 135 (01) :191-199
[9]   GLUCOSE-DEPENDENCE, CALCIUM-DEPENDENCE AND CONCENTRATION-DEPENDENCE OF ACETYLCHOLINE STIMULATION OF INSULIN RELEASE AND IONIC FLUXES IN MOUSE ISLETS [J].
GARCIA, MC ;
HERMANS, MP ;
HENQUIN, JC .
BIOCHEMICAL JOURNAL, 1988, 254 (01) :211-218
[10]  
GILON P, 1993, J BIOL CHEM, V268, P22265