Previously, we reported that distal Schaffer collaterals undergo biphasic changes in excitability during high-frequency stimulation (HFS), with an early hyper-excitability period followed by an excitability depression period. The extracellular divalent cations calcium and magnesium can regulate membrane excitability in neuronal tissue. Therefore, we hypothesized that altering the concentrations of extracellular calcium and magnesium would alter the biphasic excitability changes. We tested this hypothesis by recording distal Schaffer collateral fiber volleys in stratum radiatum of hippocampal area CA1 during 100 Hz HFS in artificial cerebral spinal fluid (ACSF) containing normal and altered concentrations of extracellular divalent cations. Our normal ACSF contained 2.0 mM calcium and 2.0 mM magnesium. We examined four solutions with altered divalent cation concentrations: (1) high-calcium/low-magnesium (3.8 mM/0.2 mM), (2) low-calcium/high-magnesium (0.2 mM/3.8 mM), (3) high-calcium/normal-magnesium (3.8 mM/2.0 mM), or (4) normal-calcium/high-magnesium (2.0 mM/10.0 mM), and assessed the effects on Schaffer collateral responses. Increasing or decreasing extracellular calcium enhanced or reduced (respectively) the early hyper-excitable period whereas increasing extracellular magnesium reduced the later excitability depression. Because these results might be explained by altered calcium influx through voltage-gated calcium (Ca_V) channels, we tested Ca_V blockers (ω-agatoxin IVA, ω-conotoxin-GVIA, cadmium), but observed no effects on responses during HFS. Some of the effects of altered divalent cation concentration may be explained by altered membrane surface charge. Although this mechanism does not completely explain our findings, calcium influx through Ca_V channels is not required.

以前，我们报道了远端 Schaffer 侧支在高频刺激 (HFS) 期间的兴奋性发生双相变化，早期的过度兴奋期随后是兴奋性抑制期。细胞外二价阳离子钙和镁可以调节神经元组织中的膜兴奋性。因此，我们假设改变细胞外钙和镁的浓度会改变双相兴奋性变化。我们通过在含有正常和改变浓度的细胞外二价阳离子的人工脑脊液 (ACSF) 中记录 100 Hz HFS 期间海马区 CA1 辐射层中的远端 Schaffer 侧支纤维齐射来验证这一假设。我们正常的 ACSF 含有 2.0 mM 钙和 2.0 mM 镁。我们检查了四种二价阳离子浓度改变的溶液：(1) 高钙/低镁 (3.8 mM/0.2 mM)，(2) 低钙/高镁 (0.2 mM/3.8 mM)，(3) 高-钙/正常镁 (3.8 mM/2.0 mM)，或 (4) 正常钙/高镁 (2.0 mM/10.0 mM)，并评估对 Schaffer 侧支反应的影响。增加或减少细胞外钙（分别）增强或减少了早期的过度兴奋期，而增加细胞外的镁减少了后期的兴奋性抑制。因为这些结果可能是通过电压门控钙（Ca 并评估了对 Schaffer 附带反应的影响。增加或减少细胞外钙（分别）增强或减少了早期的过度兴奋期，而增加细胞外的镁减少了后期的兴奋性抑制。因为这些结果可能是通过电压门控钙（Ca 并评估了对 Schaffer 附带反应的影响。增加或减少细胞外钙（分别）增强或减少了早期的过度兴奋期，而增加细胞外的镁减少了后期的兴奋性抑制。因为这些结果可能是通过电压门控钙（Ca_V ) 通道，我们测试了 Ca _V阻滞剂（ω-agatoxin IVA、ω-conotoxin-GVIA、镉），但在 HFS 期间没有观察到对反应的影响。改变的二价阳离子浓度的一些影响可以通过改变的膜表面电荷来解释。虽然这种机制不能完全解释我们的发现，但不需要通过 Ca _V通道的钙流入。