Petersen C C, Toescu E C, Petersen O H
MRC Secretory Control Research Group, Physiological Laboratory, University of Liverpool, UK.
EMBO J. 1991 Mar;10(3):527-33. doi: 10.1002/j.1460-2075.1991.tb07979.x.
Agonist-specific cytosolic Ca2+ oscillation patterns can be observed in individual cells and these have been explained by the co-existence of separate oscillatory mechanisms. In pancreatic acinar cells activation of muscarinic receptors typically evokes sinusoidal oscillations whereas stimulation of cholecystokinin (CCK) receptors evokes transient oscillations consisting of Ca2+ waves with long intervals between them. We have monitored changes in the cytosolic Ca2+ concentration ([Ca2+]i) by measuring Ca2(+)-activated Cl- currents in single internally perfused mouse pancreatic acinar cells. With minimal intracellular Ca2+ buffering we found that low concentrations of both ACh (50 nM) and CCK (10 pM) evoked repetitive short-lasting Ca2+ spikes of the same duration and frequency, but the probability of a spike being followed by a longer and larger Ca2+ wave was low for ACh and high for CCK. The probability that the receptor-evoked shortlasting Ca2+ spikes would initiate more substantial Ca2+ waves was dramatically increased by intracellular perfusion with solutions containing high concentrations of the mobile low affinity Ca2+ buffers citrate (10-40 mM) or ATP (10-20 mM). The different Ca2+ oscillation patterns normally induced by ACh and CCK would therefore appear not to be caused by separate mechanisms. We propose that specific receptor-controlled modulation of Ca2+ signal spreading, either by regulation of Ca2+ uptake into organelles and/or cellular Ca2+ extrusion, or by changing the sensitivity of the Ca2(+)-induced Ca2+ release mechanism, can be mimicked experimentally by different degrees of cytosolic Ca2+ buffering and can account for the various cytosolic Ca2+ spike patterns.
在单个细胞中可以观察到激动剂特异性的胞质Ca2+振荡模式，这些模式已通过单独振荡机制的共存得到解释。在胰腺腺泡细胞中，毒蕈碱受体的激活通常会引起正弦振荡，而胆囊收缩素（CCK）受体的刺激则会引起由Ca2+波组成的瞬态振荡，它们之间间隔较长。我们通过测量单个内部灌注的小鼠胰腺腺泡细胞中Ca2(+)-激活的Cl-电流来监测胞质Ca2+浓度（[Ca2+]i）的变化。在最小化细胞内Ca2+缓冲的情况下，我们发现低浓度的乙酰胆碱（ACh，50 nM）和CCK（10 pM）都会引起持续时间和频率相同的重复性短时间Ca2+尖峰，但ACh之后跟随更长、更大Ca2+波的概率较低，而CCK的概率较高。通过用含有高浓度可移动低亲和力Ca2+缓冲剂柠檬酸盐（10 - 40 mM）或ATP（10 - 20 mM）的溶液进行细胞内灌注，受体诱发的短时间Ca2+尖峰引发更大量Ca2+波的概率显著增加。因此，通常由ACh和CCK诱导的不同Ca2+振荡模式似乎不是由单独的机制引起的。我们提出，通过调节Ca2+摄取到细胞器和/或细胞Ca2+外排，或通过改变Ca2(+)-诱导的Ca2+释放机制的敏感性，对Ca2+信号传播进行的特定受体控制调节，可以通过不同程度的胞质Ca2+缓冲在实验中模拟，并且可以解释各种胞质Ca2+尖峰模式。
