ROLE OF HCO3- IONS IN DEPOLARIZING GABA-A RECEPTOR-MEDIATED RESPONSES IN PYRAMIDAL CELLS OF RAT HIPPOCAMPUS
ROLE OF HCO3- IONS IN DEPOLARIZING GABA-A RECEPTOR-MEDIATED RESPONSES IN PYRAMIDAL CELLS OF RAT HIPPOCAMPUS
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DOI：
10.1152/jn.1993.69.5.1541
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发表时间：
1993-05-01
影响因子：
2.5
通讯作者：
TEYLER, TJ
中科院分区：
文献类型：
--
作者：
GROVER, LM;LAMBERT, NA;TEYLER, TJ
1. GABA（A）受体激活可在CA 1区锥体细胞产生超极化和去极化反应。超极化反应由Cl-电导介导，但去极化反应的离子基础尚不清楚。我们比较了由突触释放的γ-氨基丁酸[GABA;去极化抑制性突触后电位（dIPSP）]诱导的GABA（A）受体介导的去极化与由外源性GABA产生的去极化（GABA反应）。短串高频（200 Hz）刺激用于产生dIPSP。我们发现，外源性GABA刺激和去极化反应所产生的dIPSPs都伴随着电导的增加，并且具有相似的逆转电位，表明这两种反应的离子基础相似.我们希望确定HCO 3电流是否有助于GABA（A）介导的去极化。我们发现，dIPSPs和去极化GABA的反应是敏感的灌注与HCO 3-无介质。这些数据的解释是复杂的混合性质的反应：dIPSPs总是伴随着传统的，Cl-介导的快速超极化IPSPs（fIPSPs），和响应外源性GABA通常包括双相超极化和去极化反应。然而，有时可能引起对GABA的反应，表现为纯粹的去极化（双相去极化GABA反应）。我们分析了单相去极化GABA反应，发现当切片灌注无HCO 3介质时，反转电位没有变化。我们还从CA 1锥体细胞进行了全细胞记录，试图减少[HCO 3-]i，并比较了单相去极化GABA反应的逆转电位与细细胞内微电极记录的类似反应。我们没有发现反转电位的差异。我们还研究了碳酸酐酶抑制剂乙酰唑胺（ACTZ）对去极化GABA反应的影响。ACTZ降低了这些反应，但不改变其逆转潜力。不含HCO 3的培养基对GABA（A）受体介导的反应没有特异性影响。GABA（B）受体介导的慢IPSP（sIPSP）也减少，兴奋性突触后电位（EPSP）也减少。场电位和自发fIPSPs的分析表明，突触前兴奋性降低灌注与HCO 3-自由介质。此外，在无HCO 3的培养液中，锥体细胞的输入阻力降低. GABA（A）受体介导的去极化对无HCO 3介质的敏感性可以通过突触前兴奋性的降低和突触后神经元静息电导的增加来解释。突触前兴奋性降低和静息输入阻力也可能是无HCO 3介质中快IPSP、慢IPSP和EPSP减少的原因。我们认为，这些非特异性的影响HCO 3-无介质可能是一个胞外酸化的后果。这些数据并没有提供令人信服的证据参与的HCO 3-电导的产生dIPSPs和去极化GABA的反应。
1. Activation of GABA(A) receptors can produce both hyperpolarizing and depolarizing responses in CA1 pyramidal cells. The hyperpolarizing response is mediated by a Cl- conductance, but the ionic basis of the depolarizing response is not clear. We compared the GABA(A) receptor-mediated depolarizations induced by synaptically released gamma-aminobutyric acid [GABA; depolarizing inhibitory postsynaptic potentials (dIPSPs)] with those produced by exogenous GABA (depolarizing GABA responses). Short trains of high-frequency (200 Hz) stimuli were used to generate dIPSPs. We found that dIPSPs generated by trains of stimuli and depolarizing responses to exogenous GABA were accompanied by a conductance increase and had a similar reversal potential, indicating a similar ionic basis for both responses.2. We wished to determine whether an HCO3- current contributed to the GABA(A)-mediated depolarizations. We found that dIPSPs and depolarizing GABA responses were sensitive to perfusion with HCO3--free medium. Interpretation of these data was complicated by the mixed nature of the responses: dIPSPs were invariably accompanied by conventional, Cl--mediated fast hyperpolarizing IPSPs (fIPSPs), and response to exogenous GABA usually consisted of biphasic hyperpolarizing and depolarizing responses. However, it was sometimes possible to elicit responses to GABA that appeared purely depolarizing (monophasic depolarizing GABA responses).3. We analyzed monophasic depolarizing GABA responses and found no change in reversal potential when slices were perfused with HCO3--free medium. We also made whole-cell recordings from CA1 pyramidal cells, attempting to reduce [HCO3-]i, and compared the reversal potential for monophasic depolarizing GABA responses with similar responses recorded with fine intracellular microelectrodes. We found no difference in reversal potential. We also examined effects of the carbonic anhydrase inhibitor acetazolamide (ACTZ) on depolarizing GABA responses. ACTZ reduced these responses but did not change their reversal potential.4. Effects of HCO3--free medium were not specific to GABA(A) receptor-mediated responses. GABA(B) receptor-mediated slow IPSPs (sIPSPs) were also reduced, as were excitatory postsynaptic potentials (EPSPs). Analyses of field potentials and spontaneous fIPSPs suggested a decrease in presynaptic excitability during perfusion with HCO3--free medium. In addition, pyramidal cells showed decreased input resistance when perfused with HCO 3--free medium.5. The sensitivity of GABA(A) receptor-mediated depolarizations to HCO3--free medium can be explained by a decrease in presynaptic excitability and an increased resting conductance in postsynaptic neurons. Reduced presynaptic excitability and resting input resistance are also likely causes of the reduction in fast IPSPs, slow IPSPs, and EPSPs in HCO3--free medium. We suggest that these nonspecific effects of HCO3--free medium may be a consequence of an extracellular acidification. These data do not provide convincing evidence for involvement of an HCO3- conductance in the generation of dIPSPs and depolarizing GABA responses.