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

Abstract.

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 Müller cells to investigate Ba²⁺ and Na⁺ currents through high-voltage-activated (HVA) channels, and in rabbit Müller 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 µM arachidonic acid reduced the peak LVA and HVA currents by approximately 70%. A 50% reduction of LVA currents was achieved at 4.7 µM. 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 µM 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 Müller cell function during pathological conditions in which arachidonic acid levels are elevated and may participate in the cellular action of neurotransmitters.