Calabresi P, Centonze D, Pisani A, Bernardi G
Clinica Neurologica, Universita di Roma Tor Vergata, Dip. Sanita, Rome, Italy.
J Cereb Blood Flow Metab. 1997 Oct;17(10):1121-6. doi: 10.1097/00004647-199710000-00014.
We have studied the possible mechanisms underlying the decrease of excitatory transmission induced by glucose deprivation by using electrophysiological recordings in corticostriatal slices. Extracellular field potentials were recorded in the striatum after cortical stimulation; these potentials were progressively reduced by glucose deprivation. The reduction started 5 minutes after the onset of aglycemia. The field potential was fully suppressed after 40 minutes of glucose deprivation. After the washout of the aglycemic solution only a partial recovery was observed. Aglycemia also induced a delayed inward current during single-microelectrode voltage-clamp recordings from spiny neurons. This inward current was coupled with an increased membrane conductance. The A1 adenosine receptor antagonists, 8-cyclopentyl-1,3-dimethylxanthine (CPT, 1 micromol/L) and 1,3-dipropyl-8-cyclopentylxanthine (CPX, 300 nmol/L), significantly reduced the aglycemia-induced decrease of field potential amplitude. Moreover, in the presence of CPT and CPX, a full recovery of the field potential amplitude after the interruption of the aglycemic solution was observed. Conversely, these antagonists affected neither the inward current nor the underlying conductance increase produced by glucose deprivation. The ATP-sensitive potassium channel blockers glibenclamide (10 micromol/L) and glipizide (100 nmol/L) had no effect on the aglycemia-induced decrease of the field potential amplitude. We suggest that endogenous adenosine, but not ATP-dependent potassium channels, plays a significant role in the aglycemia-induced depression of excitatory transmission at corticostriatal synapses probably through a presynaptic mechanism. Moreover, adenosine is not involved in the postsynaptic changes induced by glucose deprivation in spiny striatal neurons.
我们通过在皮质纹状体切片中进行电生理记录，研究了葡萄糖剥夺诱导兴奋性传递降低的潜在机制。在皮质刺激后记录纹状体中的细胞外场电位；这些电位会因葡萄糖剥夺而逐渐降低。低血糖开始5分钟后电位开始降低。葡萄糖剥夺40分钟后场电位被完全抑制。在洗去无糖溶液后，仅观察到部分恢复。低血糖还在棘状神经元的单微电极电压钳记录期间诱导了延迟内向电流。这种内向电流与膜电导增加相关联。A1腺苷受体拮抗剂8-环戊基-1,3-二甲基黄嘌呤（CPT，1微摩尔/升）和1,3-二丙基-8-环戊基黄嘌呤（CPX，300纳摩尔/升）显著降低了低血糖诱导的场电位幅度降低。此外，在存在CPT和CPX的情况下，观察到在无糖溶液中断后场电位幅度完全恢复。相反，这些拮抗剂既不影响内向电流，也不影响由葡萄糖剥夺产生的潜在电导增加。ATP敏感性钾通道阻滞剂格列本脲（10微摩尔/升）和格列吡嗪（100纳摩尔/升）对低血糖诱导的场电位幅度降低没有影响。我们认为内源性腺苷而非ATP依赖性钾通道，可能通过突触前机制在低血糖诱导的皮质纹状体突触兴奋性传递抑制中起重要作用。此外，腺苷不参与葡萄糖剥夺在棘状纹状体神经元中诱导的突触后变化。
