The activity of a transient potassium current in retinal glial (Müller) cells depends on extracellular calcium.
The modulating effects of varying extracellular concentrations of Ca2+ ([Ca2+]e) and of other divalent cations on the fast transient (A-type) K+ current (I(A)) of freshly isolated Muller glial cells from rabbit and human retinae were studied with the whole-cell patch-clamp method. The I(A) of Miller cells was voltage-independently blocked by extracellular 4-aminopyridine (4AP) with a 50 % reduction achieved at 0.94 mM 4AP. The I(A) amplitude was elevated by increased extracellular [K+]. Elevation of the [Ca2+]e had three effects on the glial I(A): (i) it concentration-dependently shifted both the activation and inactivation curves towards less negative membrane potentials, (ii) it increased the peak current amplitude, and (iii) it slowed down the activation and inactivation kinetics. Particularly at depolarized membrane potentials, the I(A) was enlarged and broadened when the [Ca2+]e was increased. Various divalent cations also exerted these effects, although at different concentrations. While Zn2+, Cd2+, Cu2+ and Pb2+ modulated the I(A) in the micromolar range, Mg2+ and Ba2+ had effects in the millimolar range. Extracellular acidification produced a positive shift in the voltage dependence of I(A) gating. However, alterations of the extracellular pH did not abolish the Ca2+ effects on I(A); this indicates that protons and Ca2+ ions mediate their effects on glial K(A) channels by different mechanisms or binding sites, respectively. Physiological (i.e., activity-dependent) changes of the extracellular concentration of divalent cations and of the extracellular pH should influence the retinal excitability via modulation of glial K+ currents. The activation of glial I(A) by divalent cations at depolarized voltages supports a repolarization and, therefore, the maintainance of a hyperpolarized glial membrane potential during periods of increased neuronal activity.
Bringmann
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Paul Flechsig Institute of Brain Research, Department of Neurophysiology, University of Leipzig, Germany. bria@server3.medizin.uni-leipzig.de
Schopf
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Faude
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Skatchkov
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Enzmann
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Reichenbach
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D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002413:Cations, Divalent / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051036:Large-Conductance Calcium-Activated Potassium Channels; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated; D011817:Rabbits; D012160:Retina / Q000166:cytology / Q000378:metabolism*; D013096:Spermine / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology
D002413:Cations, Divalent; D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D013096:Spermine; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D011188:Potassium; D002118:Calcium