Na+ currents through Ca2+ channels in human retinal glial (Müller) cells

Purpose. To detect the presence of voltage-gated Ca 2+ channels in the plasma membranes of freshly isolated Müller glial cells from the human retina and their modulation by GABA B receptor agonists. Methods. Whole cell voltage-clamp recordings were made to study Ca 2+, Ba 2+, and Na + currents through voltage-gated Ca 2+ channels. Results. The vast majority of the investigated cells displayed no resolvable currents through Ca 2+ channels when Ca 2+ ions (2 mM) were present in the extracellular solution. Small-amplitude inwardly directed currents (~0.6 pA/pF) were detected when Ba 2+ ions (20 mM) were used as charge carrier. However, when Na + ions were used as charge carrier in divalent cation-free external solution, currents of large amplitudes (~7.5 pA/pF) through voltage-gated Ca 2+ channels were detected. Human Müller cells displayed currents through both transient, low voltage-activated Ca 2+ channels and long-lasting, high voltage-activated channels. The Na + fluxes through low voltage-activated Ca 2+ channels were inhibited in a voltage-independent manner in the presence of GABA B receptor agonists. Conclusions. Human Müller glial cells express different kinds of voltage-gated Ca 2+ channels in their plasma membranes that can be activated only under certain physiological or pathophysiological conditions. The record of Na + fluxes in divalent cation-free solutions may be a technique to detect the presence of “hidden” voltage-gated Ca 2+ channels in Müller glial cells.

[1]  S. Chiu,et al.  N-Type Calcium Channels and Their Regulation by GABABReceptors in Axons of Neonatal Rat Optic Nerve , 1999, The Journal of Neuroscience.

[2]  X. Yang,et al.  GABA(B) receptors in Müller cells of the bullfrog retina. , 1999, Neuroreport.

[3]  H. Vaudry,et al.  GABA inhibits endozepine release from cultured rat astrocytes , 1999, Glia.

[4]  N. Matsuki,et al.  A potential role of Ras-mediated signal transduction for the enhancement of depolarization-induced Ca2+ responses in hippocampal neurons by basic fibroblast growth factor. , 1998, Brain research. Developmental brain research.

[5]  K. S. Lee,et al.  Ionic mechanism of ibutilide in human atrium: evidence for a drug-induced Na+ current through a nifedipine inhibited inward channel. , 1998, The Journal of pharmacology and experimental therapeutics.

[6]  T. Pannicke,et al.  Comparison between functional characteristics of healthy and pathological human retinal Müller glial cells. , 1997, Survey of ophthalmology.

[7]  A. Reichenbach,et al.  Loss of inwardly rectifying potassium currents by human retinal glial cells in diseases of the eye , 1997, Glia.

[8]  P. Agostinho,et al.  Oxidative stress affects the selective ion permeability of voltage-sensitive Ca2+ channels in cultured retinal cells , 1997, Neuroscience Research.

[9]  P. Kostyuk,et al.  Two types of low‐voltage‐activated Ca2+ channels in neurones of rat laterodorsal thalamic nucleus. , 1997, The Journal of physiology.

[10]  T. Pannicke,et al.  Sodium Current Amplitude Increases Dramatically in Human Retinal Glial Cells during Diseases of the Eye , 1996, The European journal of neuroscience.

[11]  A. Bhattacharjee,et al.  Abnormally Expressed Low-Voltage-Activated Calcium Channels in β-Cells From NOD Mice and a Related Clonal Cell Line , 1996, Diabetes.

[12]  E. Newman,et al.  The Müller cell: a functional element of the retina , 1996, Trends in Neurosciences.

[13]  D. Puro,et al.  Characterization of an L-type calcium channel expressed by human retinal Müller (glial) cells. , 1996, Brain research. Molecular brain research.

[14]  Jean -Pierre Gomez,et al.  Developmental changes in Ca2+ currents from newborn rat cardiomyocytes in primary culture , 1994, Pflügers Archiv.

[15]  T. I. Chao,et al.  Na+ channels of Müller (glial) cells isolated from retinae of various mammalian species including man , 1994, Glia.

[16]  M. Joëls,et al.  Low-threshold calcium current in dendrites of the adult rat hippocampus , 1993, Neuroscience Letters.

[17]  N. Matsuki,et al.  Effect of fibroblast growth factors on calcium currents in acutely isolated neuronal cells from rat ventromedial hypothalamus , 1993, Neuroscience Letters.

[18]  D. D. Fraser,et al.  Low-threshold transient calcium current in rat hippocampal lacunosum- moleculare interneurons: kinetics and modulation by neurotransmitters , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[19]  T. Mano,et al.  Modulation of calcium channels in human retinal glial cells by basic fibroblast growth factor: a possible role in retinal pathobiology , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[20]  M. Lacey,et al.  Electrophysiological characterization of potent agonists and antagonists at pre‐ and postsynaptic GABAB receptors on neurones in rat brain slices , 1990, British journal of pharmacology.

[21]  E. Costa,et al.  Baclofen inhibits with high affinity an L-type — like voltage-dependent calcium channel in cerebellar granule cell cultures , 1990, Neuropharmacology.

[22]  B. Barres,et al.  Calcium current in cortical astrocytes: induction by cAMP and neurotransmitters and permissive effect of serum factors , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[23]  P. Kostyuk,et al.  Dihydropyridine‐sensitive low‐threshold calcium channels in isolated rat hypothalamic neurones. , 1989, The Journal of physiology.

[24]  M. Nowycky,et al.  Kinetic and pharmacological properties distinguishing three types of calcium currents in chick sensory neurones. , 1987, The Journal of physiology.

[25]  E. Newman.  Voltage-dependent calcium and potassium channels in retinal glial cells , 1985, Nature.

[26]  W. Almers,et al.  Non‐selective conductance in calcium channels of frog muscle: calcium selectivity in a single‐file pore. , 1984, The Journal of physiology.

[27]  A. Verkhratsky,et al.  Glial calcium: homeostasis and signaling function. , 1998, Physiological reviews.

[28]  B. Bettler,et al.  Expression cloning of GABA(B) receptors uncovers similarity to metabotropic glutamate receptors. , 1997, Nature.

[29]  D. Puro.  Calcium Channels of Human Retinal Glial Cells , 1994 .

[30]  R. Tsien,et al.  Mechanism of ion permeation through calcium channels , 1984, Nature.