Arachidonic acid-induced inhibition of Ca2+ channel currents in retinal glial (Müller) cells.

Background: Arachidonic acid is a second messenger that has been implicated in several pathological conditions in nervous tissues. The present study was carried out to determine whether the second messenger arachidonic acid modulates currents through voltage-gated Ca2+ channels in freshly isolated Müller glial cells.

Methods: Whole-cell voltage-clamp recordings were made in human Muller cells to investigate Ba2+ and Na+ currents through high-voltage-activated (HVA) channels, and in rabbit Muller cells to study Na+ currents through low-voltage-activated (LVA) channels.

Results: Extracellular application of arachidonic acid reversibly and dose-dependently depressed the amplitude of both LVA (rabbit cells) and HVA currents (human cells). 10 microM arachidonic acid reduced the peak LVA and HVA currents by approximately 70%. A 50% reduction of LVA currents was achieved at 4.7 microM. The block of HVA and LVA currents was not accompanied by alterations in the voltage dependences of current activation and inactivation. A similar reduction of the currents was achieved by 20 microM eicosatetraynoic acid.

Conclusion: Since eicosatetraynoic acid mimics the effects of arachidonic acid, it is assumed that arachidonic acid itself rather than its degradation products modulates glial Ca2+ channel activity. This Ca2+ channel inhibition may stabilize Muller cell function during pathological conditions in which arachidonic acid levels are elevated and may participate in the cellular action of neurotransmitters.