Duffy S, MacVicar B A
Department of Neuroscience, University of Calgary, Alberta, Canada.
Neuroscience. 1994 Jul;61(1):51-61. doi: 10.1016/0306-4522(94)90059-0.
Potassium depolarization can increase the intracellular ionized calcium concentration ([Ca2+]i) of cultured astrocytes, but it is not known if astrocytes that have matured in the intact CNS also exhibit voltage-dependent [Ca2+]i signalling. To address this issue, fluorometric measurements of [Ca2+]i were obtained from astrocytes acutely isolated from young adult rat hippocampus. In control artificial cerebrospinal fluid containing 5 mM [K+]o, average resting [Ca2+]i was 195 nM. Elevation of [K+]o to 50 mM caused [Ca2+]i to increase 150 nM to 1 microM above resting levels. The threshold [K+]o necessary to evoke an elevation in [Ca2+]i was 20-25 mM, and the magnitude of the [Ca2+]i signal grew progressively with increasing [K+]o (up to 50 mM). These [Ca2+]i increases were blocked completely by removal of external Ca2+, and markedly suppressed by the calcium channel blockers verapamil (30 microM and greater) and Co2+ (1 mM). Neither reversal of Na(+)-Ca2+ exchange, nor Ca(2+)-activated Ca2+ release, nor Ca2+ influx through stretch-activated channels contributed to the [Ca2+]i increase. These results suggest that [K+]o-evoked [Ca2+]i signals are mediated by influx through voltage-gated calcium channels. In contrast to results from cultured astrocytes and acutely isolated neurons, these [Ca2+]i increases were insensitive to dihydropyridine compounds. We conclude that increases in interstitial [K+], observed in situ during several pathological conditions, trigger voltage-dependent [Ca2+]i signals in astroglial cells. This may constitute an important form of neuron-to-glial communication.
钾离子去极化可增加培养星形胶质细胞的细胞内游离钙浓度（[Ca2+]i），但尚不清楚在完整中枢神经系统中成熟的星形胶质细胞是否也表现出电压依赖性[Ca2+]i信号传导。为解决这个问题，我们从年轻成年大鼠海马体中急性分离出星形胶质细胞，对其进行[Ca2+]i的荧光测量。在含有5 mM [K+]o的对照人工脑脊液中，平均静息[Ca2+]i为195 nM。将[K+]o升高至50 mM导致[Ca2+]i比静息水平增加150 nM至1 microM。引起[Ca2+]i升高所需的阈值[K+]o为20 - 25 mM，并且[Ca2+]i信号的幅度随着[K+]o的增加（高达50 mM）而逐渐增大。这些[Ca2+]i的增加在去除细胞外Ca2+后被完全阻断，并被钙通道阻滞剂维拉帕米（30 microM及以上）和Co2+（1 mM）显著抑制。Na(+)-Ca2+交换的逆转、Ca(2+)-激活的Ca2+释放以及通过牵张激活通道的Ca2+内流均未对[Ca2+]i的增加有贡献。这些结果表明，[K+]o诱发的[Ca2+]i信号是由通过电压门控钙通道的内流介导的。与培养的星形胶质细胞和急性分离的神经元的结果相反，这些[Ca2+]i的增加对二氢吡啶化合物不敏感。我们得出结论，在几种病理情况下原位观察到的间质[K+]增加会触发星形胶质细胞中的电压依赖性[Ca2+]i信号。这可能构成神经元与胶质细胞通讯的一种重要形式。
