Alterations of potassium channel activity in retinal Müller glial cells induced by arachidonic acid

Abstract

Arachidonic acid, which is thought to be involved in pathogenetic mechanisms of the central nervous system, has been shown previously to modulate neuronal ion channels and the glutamate uptake carrier of retinal glial (Müller) cells. We have used various configurations of the patch-clamp technique to determine the effects of arachidonic acid on the K + currents of freshly isolated Müller glial cells from rabbit and human. Arachidonic acid reduced the peak amplitude of the transient (A-type) outward K + currents in a dose-dependent and reversible manner, with a 50% reduction achieved by 4.1 μM arachidonic acid. The inward rectifier-mediated currents remained unchanged after arachidonic acid application. The amplitude of the Ca 2+-activated K + outward currents (K Ca), which were blocked by 1 mM tetraethylammonium chloride and 40 nM iberiotoxin, respectively, was dose-dependently elevated by bath application of arachidonic acid. The activation curve of the K Ca currents shifted towards more negative membrane potentials. Furthermore, arachidonic acid was found to suppress inwardly directed Na + currents. In cell-attached recordings with 3 mM K + in the bath and 130 mM K + in the pipette, the K Ca channels of rabbit Müller cells displayed a linear current–voltage relation, with a mean slope conductance of 102 pS. In excised patches, the slope conductance was 220 pS (150 mM K + i/130 mM K + o). The opening probability of the K Ca channels increased during membrane depolarization and during elevation of the free Ca 2+ concentration at the intracellular face of the membrane patches. Bath application of arachidonic acid caused a reversible increase of the single-channel opening probability, as well as an increase of the number of open channels. Arachidonic acid did not affect the single-channel conductance. Since arachidonic acid also stimulates the K Ca channel activity in excised patches, the action of arachidonic acid is assumed to be independent of changes of the intracellular calcium concentration. Our results demonstrate that arachidonic acid exerts specific effects on distinct types of K + channels in retinal glial cells. In pathological cases, elevated arachidonic acid levels may contribute to prolonged Müller cell depolarizations, and to the initiation of reactive glial cell proliferation.