Huang R, Somjen G G
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Brain Res. 1997 Feb 14;748(1-2):157-67. doi: 10.1016/s0006-8993(96)01294-2.
We studied the effects of hypertonia on voltage-gated currents of freshly isolated hippocampal CA1 neurons, using open pipette whole-cell as well as gramicidin-perforated patch-clamp recording. Extracellular osmolarity (pi(o)) was raised by adding mannitol (50 or 100 mmol/l) to the bathing solution. Hypertonia depressed voltage-gated sodium, potassium and calcium currents in all trials. The threshold activation voltage of the currents did not change during hypertonic depression, but maximal activation of Ca2+ current shifted to a more negative potential, suggesting stronger depression of high- compared to low-voltage activated currents. During 30 min high pi(o) treatment (recorded with open pipette), the depression reached maximum in 10-15 min of exposure. The depression of the computed transient component of the K+ current recorded by open pipette was statistically not significant. Following hypertonic treatment recovery of the I(Na), the sustained I(K) and sustained I(Ca) were incomplete compared to control cells maintained in normal solution for an equal length of time. In hippocampal tissue slices hypertonia (+25, +50 and +100 mmol/l fructose) reversibly depressed excitatory postsynaptic currents (EPSCs). We conclude that the shutdown of membrane ion currents by elevated pi(o) is not selective, but the degree of the suppression varies among current types. Raising pi(o) in human patients, possibly combined with mild artificial acidosis, may be useful in the prevention and treatment of acute crises associated with excessive excitation or depolarization of neurons.
我们使用开放式微电极全细胞记录以及短杆菌肽穿孔膜片钳记录，研究了高渗对新鲜分离的海马CA1神经元电压门控电流的影响。通过向浴液中添加甘露醇（50或100 mmol/l）来提高细胞外渗透压（π(o)）。在所有实验中，高渗均抑制了电压门控钠、钾和钙电流。电流的阈值激活电压在高渗抑制期间未发生变化，但Ca2+电流的最大激活向更负的电位移动，表明与低电压激活电流相比，高电压激活电流受到更强的抑制。在30分钟的高π(o)处理期间（用开放式微电极记录），抑制在暴露10 - 15分钟时达到最大值。用开放式微电极记录的K+电流计算出的瞬态成分的抑制在统计学上不显著。与在等长的正常溶液中维持的对照细胞相比，高渗处理后I(Na)、持续I(K)和持续I(Ca)的恢复不完全。在海马组织切片中，高渗（+25、+50和+100 mmol/l果糖）可逆地抑制兴奋性突触后电流（EPSCs）。我们得出结论，升高π(o)导致的膜离子电流关闭并非具有选择性，而是抑制程度在不同电流类型之间有所差异。在人类患者中升高π(o)，可能联合轻度人工酸中毒，可能有助于预防和治疗与神经元过度兴奋或去极化相关的急性危机。
