Dual effects of the protein kinase inhibitor H-7 on CA1 responses in the hippocampal slice.
Dual effects of the protein kinase inhibitor H-7 on CA1 responses in the hippocampal slice.
复制标题
蛋白激酶抑制剂 H-7 对海马切片 CA1 反应的双重作用。
DOI：
10.1111/j.1749-6632.1991.tb25942.x
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发表时间：
1991
影响因子：
5.2
通讯作者：
Vallano,ML
中科院分区：
文献类型：
--
作者：
Leahy,JC;Vallano,ML
Long-term potentiation (LTP) in the hippocampus is currently one of the most attractive models for mammalian learning and memory. In the pathway from CA3 to CAI, LTP can be recorded extracellularly as an enhancement in the population excitatory postsynaptic potential (EPSP) amplitude/slope as well as the population spike amplitude, following tetanization of the Schaffer-commissural fibers. The molecular mechanisms underlying LTP remain unclear, although the induced changes in EPSP and spike potentiation may be distinct.'Recent studies employing high concentrations (300 pM) of the protein kinase inhibitor H-7 (that is, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine) support a role for calcium-dependent kinases in both the induction and maintenance of EPSP potentiation.* In a separate study, however, 100 pM H-7 neither prevented the induction of synaptic LTP nor abolished previously established LTP. 3 Additionally, low concentrations (10-100 pM) of H-7 have been shown to enhance the CAI population spike amplitude and produce multiple responses., The goal of this study was to examine whether H-7 exhibits concentration-dependent effects on more than one pathway, which may explain the apparent discrepancies described above.Experiments were performed using the in vitro hippocampal slice preparation from young (1 5-60 days postnatal) Sprague-Dawley rats. Hippocampal slices (400 pm) were placed in a submersion chamber and perfused at 4 ml/min with medium continuously bubbled with 95% 0,/5% CO, at 33-34" C, pH 7.4. Standard medium contained 124 mM NaCI, 5 mM KCl, 1.25 mM KH, PO,, 2.0 mM MgSO,, 2.0 mM CaCI,, 25 mM NaHCO,, and 10 mM glucose. Extracellular CAI pyramidal cell responses were recorded with glass micropipettes containing 2 M NaCI, using conventional recording procedures. The recording electrode was positioned in stratum pyramidale, with bipolar stimulating electrodes placed on either side in stratum radiatum. The stimulus intensity at both sites was adjusted to evoke a population spike amplitude of about 1.0-1.5 mV (that is, 20-30% of maximum amplitude). Initially, test stimuli (0.1-msec pulses) were delivered to both pathways at a rate of 1/20 sec (10-sec interstimulus interval) for 10-15 min to establish a baseline response. Following the test period, a high-frequency stimulus (HFS) was delivered to the S1 pathway (100 Hz, 1.0 sec, 0.2-msec pulses). The effect of the HFS on the population spike amplitude was then monitored in both pathways for 20 min, employing the initial test stimulus pattern. At this point, the standard medium was replaced with one containing either 50 pM or 300 pM H-7 (Sigma). The medium containing H-7 was administered for 15-20 min followed by washout with standard medium for 30-60 min. Examples of the time course of the effect of H-7 on CAI responses in control and potentiated pathways are shown in FIGURE 1. Following the HFS in the S1 pathway,
