ASTROGLIAL MODULATION OF TRANSIENT POTASSIUM CURRENT DEVELOPMENT IN CULTURED MOUSE HIPPOCAMPAL-NEURONS

被引:57
作者
WU, RL [1 ]
BARISH, ME [1 ]
机构
[1] BECKMAN RES INST CITY HOPE, DIV NEUROSCI, DUARTE, CA 91010 USA
关键词
A-CURRENT; D-CURRENT; K-CURRENT; POTASSIUM CURRENTS; NEURONAL DEVELOPMENT; ION CHANNELS; ASTROGLIA; NEURON-GLIA INTERACTIONS;
D O I
10.1523/JNEUROSCI.14-03-01677.1994
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Hippocampal neurons exhibit three voltage-gated potassium currents, two transient currents and a delayed rectifier, that influence numerous aspects of electrogenesis including action potential duration and accommodation to sustained depolarization. These currents, termed A-, D-, and K-currents, respectively, can be distinguished based on kinetics, steady state inactivation characteristics, and sensitivity to 4-aminopyridine (see Wu and Barish, 1992b). We have compared the voltage-gated potassium currents in voltage-clamped pyramidally shaped cultured hippocampal neurons growing on or touching glial fibrillary acidic protein-expressing astroglia (termed on-glia or touching-glia neurons, respectively) with those in similar neurons growing directly on a coated glass substrate (termed off-glia neurons). We observed differences in the wave forms of total potassium current that correlated with the extent of astroglial contact. After 5-7 d in culture, A-current amplitude in off-glia neurons was approximately 19% of that of neurons growing in the normal (for culture) on-glia configuration. D-current amplitude tended to be larger in these off-glia neurons. Neurons in contact with astroglia had greater membrane area than off-glia neurons. Comparison of current densities (current at a fixed voltage normalized to capacitance and expressed in units of pA/pF) indicated that A-currents were the major component of transient potassium current in on- and touching-glia neurons, while D-currents were more dominant in off-glia neurons. Astroglia influenced membrane currents by a surface- or extracellular matrix-associated mechanism, rather than by free diffusion of a soluble factor, as differences were observed between closely adjacent neurons on the same coverslip. Living glia were required, as potassium currents in neurons grown on dried or methanol-fixed glia resembled those of off-glia neurons. On-glia neurons in cultures treated with an RNA synthesis inhibitor [DRB (5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole)] for 5-7 d had reduced whole-cell capacitance and A-current amplitude. This effect was localized to DRB actions on underlying astroglia, not on the neurons. Action potentials elicited by current injection varied with astroglial contact. In on-glia neurons with relatively larger A-currents a delay was seen in the onset of firing after depolarization. In contrast, action potentials in off-glia neurons rose smoothly after initiation of depolarization. We conclude that astrocytes modulate the appearance of transient potassium currents in hippocampal pyramidal neurons by inducing development of A-current. Increased A-current amplitude was associated with an increase in membrane area; this observation suggests the possibility that glia promote insertion of A-current-rich membrane. Signals appear to pass from astroglia to neurons by contact or short-range diffusion. We propose astroglial-induced plasticity of A-current as a mechanism for long-term modulation of hippocampal neuron excitability.
引用
收藏
页码:1677 / 1687
页数:11
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