Farnesol modulates membrane currents in human retinal glial cells.

Abstract

Farnesol, a C(15) natural isoprenoid, exerts complex modulating effects on the membrane permeability of human retinal glial (Müller) cells. Several glial cationic currents were examined. At low micromolar concentrations, farnesol reduced the amplitudes of all fast and depolarization-activated membrane currents expressed by Müller cells, that is, currents through 1) transient low-voltage-activated (LVA; IC(50) = 2.2 microM), 2) sustained high-voltage-activated Ca(2+) channels (HVA; IC(50) = 1.2 microM), 3) fast Na(+) channels (IC(50) = 9.0 microM), and 4) transient (A-type) K(+) channels (IC(50) = 4.7 microM). Furthermore, farnesol shifted the activation of LVA and HVA currents to more depolarized potentials by 21.3 +/- 7.4 mV and 8.3 +/- 4.5 mV, respectively. On the other hand, neither inwardly rectifying nor iberiotoxin-sensitive calcium-activated K(+) currents were affected by farnesol. Therefore, farnesol is assumed to be a biologically active substance that regulates ion channel activity in the glial cell membrane. Depressing rapid changes of the membrane potential and supporting a stable hyperpolarized status of the glial cells may enhance the efficiency of crucial glial functions such as extracellular K(+) clearance and neurotransmitter uptake.