Nachshen D A, Blaustein M P
Biophys J. 1979 May;26(2):329-34. doi: 10.1016/S0006-3495(79)85253-4.
The effects of low pH, and of alkaline earth cations, were examined on calcium uptake by pinched-off nerve terminals (synaptosomes). This uptake appears to be mediated by voltage-sensitive Ca channels (J. Physiol. 247:617, 1975). Ca uptake was measured in low (5 mM) or high (77 mM) potassium media. The extra uptake promoted by depolarizing (K-rich) media was almost maximal at pH 7.5, and decreased as the pH was lowered. Data relating depolarization-induced 45Ca uptake to pH fit a titration curve with a pKa approximately 6. Experiments in which Ca concentration and pH were both varied indicated that Ca2+ and H+ compete for a common binding site. Inhibition of depolarization-induced 45Ca uptake by the alkaline earth cations was studied to determine the apparent binding sequence for these cations in the Ca channels: Ca greater than Sr greater than Ba greater than Mg. This sequence resembles that observed for block of Ca channels in other preparations. The apparent binding sequence of the alkaline earth cations and the apparent pKa (approximately 6) of the Ca-binding site indicate that the Ca channel is a "high field strength" system. Protonation of a Ca channel binding site could explain the inhibitory effect of low pH on Ca-dependent neurotransmitter release (cf. Del Castillo et al., J. Cell. Comp. Physiol. 59:35, 1962).
研究了低pH值以及碱土金属阳离子对夹断神经末梢（突触体）摄取钙的影响。这种摄取似乎是由电压敏感的钙通道介导的（《生理学杂志》247:617, 1975）。在低（5 mM）或高（77 mM）钾培养基中测量钙摄取。去极化（富含钾）培养基促进的额外摄取在pH 7.5时几乎达到最大值，并随着pH值降低而减少。将去极化诱导的45Ca摄取与pH值相关的数据拟合为pKa约为6的滴定曲线。钙浓度和pH值均变化的实验表明，Ca2+和H+竞争一个共同的结合位点。研究了碱土金属阳离子对去极化诱导的45Ca摄取的抑制作用，以确定这些阳离子在钙通道中的表观结合顺序：Ca > Sr > Ba > Mg。该顺序类似于在其他制剂中观察到的钙通道阻断顺序。碱土金属阳离子的表观结合顺序和钙结合位点的表观pKa（约为6）表明钙通道是一个“高场强”系统。钙通道结合位点的质子化可以解释低pH值对钙依赖性神经递质释放的抑制作用（参见德尔卡斯蒂略等人，《细胞与比较生理学杂志》59:35, 1962）。
