Heterogeneity of Astrocyte Resting Membrane Potentials and Intercellular Coupling Revealed by Whole-Cell and Gramicidin-Perforated Patch Recordings from Cultured Neocortical and Hippocampal Slice Astrocytes

Journal of Neuroscience - Tập 17 Số 18 - Trang 6850-6863 - 1997
Guy M. McKhann1, Raimondo D’Ambrosio1, Damir Janigro1,2
1Departments of Neurological Surgery, and
2Environmental Health, University of Washington School of Medicine, Seattle, Washington 98104

Tóm tắt

Astrocytes are thought to regulate the extracellular potassium concentration by mechanisms involving both voltage-dependent and transport-mediated ion fluxes combined with intercellular communication via gap junctions. Mechanisms regulating resting membrane potential (RMP) play a fundamental role in determining glial contribution to buffering of extracellular potassium and uptake of potentially toxic neurotransmitters. We have investigated the passive electrophysiological properties of cultured neocortical astrocytes and astrocytes recorded in hippocampal slices from 18–25 d postnatal rats. These experiments revealed a wide range of astrocyte RMPs that were independent of developmental factors, length of culturing, cellular morphology, the electrophysiological techniques used (whole-cell vs perforated recording), cell-specific expression of Na+/2HCO3co-transporters, or voltage-dependent Na+channels. Exposure of cultured astrocytes to differentiation-inducing factors (such as cAMP) or inhibition of proliferation (by serum deprivation) did not significantly influence RMP. Expression of ATP-sensitive potassium channels was absent in these glia; thus, K(ATP)-related mechanisms did not contribute to cell resting potential. In both cultured and slice astrocytes, spontaneous electrophysiological changes were commonly observed. These reversible events, which resulted in differential sensitivity to potassium channel blockers (cesium and barium) and sudden current–voltage profile changes, were attributable to dynamic changes in cell-to-cell coupling, as confirmed by recordings from isolated pairs of cells. We conclude that the heterogeneity of astrocytic RMP and intercellular coupling both in culture andin situare intrinsic properties of glia that may contribute to transcellular transport of potassium. We propose a model in which spatial buffering may be facilitated by heterogeneous mechanisms controlling glial RMP in combination with dynamic changes in intercellular coupling.

Từ khóa


Tài liệu tham khảo

10.1016/0006-8993(83)90801-6

10.1038/347069a0

10.1113/jphysiol.1987.sp016361

10.1523/JNEUROSCI.09-09-03169.1989

10.1146/annurev.ne.13.030190.002301

10.1523/JNEUROSCI.11-10-03008.1991

10.1002/glia.440070403

Bordey A, Sontheimer H (1997) Post-natal development of ionic currents in rat hippocampal astrocytes in situ, J Neurophysiol, in press.

Casullo, 1987, Glial potentials in hippocampus., Can J Physiol Pharmacol, 65, 847, 10.1139/y87-136

10.1523/JNEUROSCI.09-06-02011.1989

10.1111/j.1460-9568.1995.tb01027.x

10.1523/JNEUROSCI.11-05-01421.1991

Erdemli, 1994, Guanosine diphosphate is required for activation of a glyburide, ATP and cromakalim-sensitive outward current in rat hippocampal neurons., NeuroReport, 5, 1362

10.1016/0896-6273(92)90131-V

10.1016/0166-2236(96)10046-1

10.1016/0896-6273(91)90128-M

10.1002/(SICI)1098-1136(199603)16:3<196::AID-GLIA2>3.0.CO;2-0

10.1016/0014-2999(95)00746-6

Janigro, 1988, Effects of GABA and baclofen on pyramidal cells in the developing rabbit hippocampus: an “in vitro” study., Brain Res, 469, 171, 10.1016/0165-3806(88)90180-0

Janigro, 1993, ATP-sensitive K+ channels in rat aorta and brain microvascular endothelial cells., Am J Physiol, 265, 812, 10.1152/ajpcell.1993.265.3.C812

10.1161/01.RES.75.3.528

10.1523/JNEUROSCI.17-08-02813.1997

Janigro, 1997, Endothelium-dependent regulation of cerebrovascular tone by extracellular and intracellular ATP., Am J Physiol, 42, H878

Joyner, 1973, A model simulating the hypothetical contribution of glia cells to extracellular potentials., Prog Neurobiol, 1, 227

10.1016/0013-4694(66)90024-1

Kettenmann H (1990) Chloride channels and carriers in cultured glial cells. in Chloride channels and carriers in nerve, muscle, and glial cells, eds Alvarez-Leefmans FJ Russel JM (Plenum, New York), pp 193–208.

Kimelberg HK (1990) Chloride transport across glial cell membrane. in Chloride channels and carriers in nerve, muscle, and glial cells, eds Alvarez-Leefmans FJ Russel JM (Plenum, New York), pp 159–191.

10.1002/glia.440150210

Krnjevic, 1967, Some properties of unresponsive cells in the cerebral cortex., Exp Brain Res, 3, 306, 10.1007/BF00237557

Kuffler, 1967, Neuroglial cells: physiological properties and a potassium-mediated effect of neuronal activity on the glial membrane potential., Proc R Soc Lond [Biol], 168, 1

Kuffler, 1966, Physiological properties of glial cells in the central nervous system of amphibia., J Neurophysiol, 29, 768, 10.1152/jn.1966.29.4.768

10.1523/JNEUROSCI.16-03-01219.1996

10.1002/glia.440110404

Lux HD Heinemann U Dietzel I (1986) Ionic changes and alterations in the size of extracellular space during epileptic activity. in Advances in Neurology, eds Delgado-Escueta AV Ward AA (Raven, New York), pp 619–639.

10.1002/(SICI)1098-1136(199603)16:3<285::AID-GLIA11>3.0.CO;2-W

McKhann GM, D’Ambrosio R, Janigro D (1997) Potential pitfalls in the pharmacological investigation of astrocyte ion channels and gap junctions. Soc Neurosci Abstr. vol. 22.

Newman EA (1995) Glial cell regulation of extracellular potassium. in Neuroglia, eds Kettenmann H Ransom BR (Oxford University, New York), pp 717–731.

Nicholls, 1964, Extracellular space as a pathway for exchange between blood and neurons in the CNS of the leech: ionic composition of glial cells and neurons., J Neurophysiol, 27, 645, 10.1152/jn.1964.27.4.645

O’Connor, 1994, Rat hippocampal astrocytes exhibit electrogenic sodium-bicarbonate co-transport., J Neurophysiol, 72, 2580, 10.1152/jn.1994.72.6.2580

Pappas, 1994, Depolarization-induced alkalinization (DIA) in rat hippocampal astrocytes., J Neurophysiol, 72, 2816, 10.1152/jn.1994.72.6.2816

10.1126/science.3616619

10.1002/(SICI)1098-1136(199605)17:1<72::AID-GLIA7>3.0.CO;2-9

10.1523/JNEUROSCI.03-06-01289.1983

Ransom BR (1995) Gap junctions. in Neuroglia, eds Kettenmann H Ransom BR (Oxford University, New York), pp 299–318.

Ransom, 1973, Ionic determinants of membrane potential of cells presumed to be glia in cerebral cortex of cat., J Neurophysiol, 36, 855, 10.1152/jn.1973.36.5.855

Ransom, 1973, Slow depolarization in cells presumed to be glia in cerebral cortex of cat., J Neurophysiol, 36, 869, 10.1152/jn.1973.36.5.869

Ransom, 1973, Slow hyperpolarization in cells presumed to be glia in cerebral cortex of cat., J Neurophysiol, 36, 879, 10.1152/jn.1973.36.5.879

10.1152/jn.1995.73.1.333

Ransom, 1996, Astrocytic inwardly-rectifying potassium currents are dependent on extracellular sodium ions., J Neurophysiol, 76, 626, 10.1152/jn.1996.76.1.626

Rhee, 1994, Gramicidin perforated patch-clamp technique reveals glycine-gated outward chloride currents in dissociated nucleus solitarii neurons of the rat., J Neurophysiol, 72, 1103, 10.1152/jn.1994.72.3.1103

10.1523/JNEUROSCI.16-17-05393.1996

10.1002/(SICI)1098-1136(199611)18:3<177::AID-GLIA2>3.0.CO;2-X

10.1016/0006-8993(79)90683-8

10.1002/glia.440110210

Sontheimer, 1993, Expression of voltage-activated ion channels by astrocytes and oligodendrocytes in the hippocampal slice., J Neurophysiol, 70, 1863, 10.1152/jn.1993.70.5.1863

Sontheimer, 1992, Ion channels in spinal cord astrocytes in vitro I. Transient expression of high levels of Na+ and K+ channels., J Neurophysiol, 68, 985, 10.1152/jn.1992.68.4.985

Steinhauser, 1993, Electrophysiologic characteristics of glial cells., Hippocampus, 3, 113, 10.1002/hipo.1993.4500030714

10.1016/0014-4886(71)90018-5

10.1523/JNEUROSCI.12-05-01781.1992

Vera, 1997, Inhibition of astrocyte gap junctional communication by ATP depletion is reversed by calcium sequestration., FEBS Lett, 392, 225, 10.1016/0014-5793(96)00794-6