Evaluation of mechanisms involved in regulation of intrinsic excitability by extracellular calcium in CA1 pyramidal neurons of rat.

IF 4.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Neurochemistry Pub Date : 2024-08-20 DOI:10.1111/jnc.16209
My Forsberg, Dinna Zhou, Shadi Jalali, Giorgia Faravelli, Henrik Seth, Andreas Björefeldt, Eric Hanse
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Abstract

It is well recognized that changes in the extracellular concentration of calcium ions influence the excitability of neurons, yet what mechanism(s) mediate these effects is still a matter of debate. Using patch-clamp recordings from rat hippocampal CA1 pyramidal neurons, we examined the contribution of G-proteins and intracellular calcium-dependent signaling mechanisms to changes in intrinsic excitability evoked by altering the extracellular calcium concentration from physiological (1.2 mM) to a commonly used experimental (2 mM) level. We find that the inhibitory effect on intrinsic excitability of calcium ions is mainly expressed as an increased threshold for action potential firing (with no significant effect on resting membrane potential) that is not blocked by either the G-protein inhibitor GDPβS or the calcium chelator BAPTA. Our results therefore argue that in the concentration range studied, G-protein coupled calcium-sensing receptors, non-selective cation conductances, and intracellular calcium signaling pathways are not involved in mediating the effect of extracellular calcium ions on intrinsic excitability. Analysis of the derivative of the action potential, dV/dt versus membrane potential, indicates a current shift towards more depolarized membrane potentials at the higher calcium concentration. Our results are thus consistent with a mechanism in which extracellular calcium ions act directly on the voltage-gated sodium channels by neutralizing negative charges on the extracellular surface of these channels to modulate the threshold for action potential activation.

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评估大鼠 CA1 锥体神经元细胞外钙调节固有兴奋性的机制
众所周知,细胞外钙离子浓度的变化会影响神经元的兴奋性,但这些影响是由什么机制介导的仍是一个争论不休的问题。利用大鼠海马 CA1 锥体神经元的贴片钳记录,我们研究了 G 蛋白和细胞内钙离子依赖性信号机制对改变细胞外钙离子浓度(从生理水平(1.2 mM)到常用的实验水平(2 mM))所诱发的内在兴奋性变化的贡献。我们发现,钙离子对内在兴奋性的抑制作用主要表现为动作电位发射阈值的升高(对静息膜电位无明显影响),这种作用不会被 G 蛋白抑制剂 GDPβS 或钙螯合剂 BAPTA 所阻断。因此,我们的研究结果表明,在所研究的浓度范围内,G 蛋白偶联钙传感受体、非选择性阳离子传导和细胞内钙信号途径并未参与介导细胞外钙离子对内在兴奋性的影响。对动作电位的导数 dV/dt 与膜电位的分析表明,在钙离子浓度较高时,电流转向更多的去极化膜电位。因此,我们的结果与细胞外钙离子通过中和这些通道细胞外表面的负电荷直接作用于电压门控钠通道以调节动作电位激活阈值的机制是一致的。
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来源期刊
Journal of Neurochemistry
Journal of Neurochemistry 医学-神经科学
CiteScore
9.30
自引率
2.10%
发文量
181
审稿时长
2.2 months
期刊介绍: Journal of Neurochemistry focuses on molecular, cellular and biochemical aspects of the nervous system, the pathogenesis of neurological disorders and the development of disease specific biomarkers. It is devoted to the prompt publication of original findings of the highest scientific priority and value that provide novel mechanistic insights, represent a clear advance over previous studies and have the potential to generate exciting future research.
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