Farnesol modulates membrane currents in human retinal glial cells

Farnesol, a C-15 natural isoprenoid, exerts complex modulating effects on t he membrane permeability of human retinal glial (Muller) cells. Several gli al cationic currents were examined. At low micromolar concentrations, farne sol reduced the amplitudes of all fast and depolarization-activated membran e currents expressed by Muller cells, that is, currents through 1) transien t low-voltage-activated (LVA; IC50 = 2.2 muM), 2) sustained high-voltage-ac tivated Ca2+ channels (HVA; IC50 = 1.2 muM), 3) fast Na+ channels (IC50 = 9 .0 muM), and 4) transient (A-type) K+ channels (IC50 = 4.7 muM). Furthermor e, farnesol shifted the activation of LVA and HVA currents to more depolari zed 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-a ctivated K+ currents were affected by farnesol. Therefore, farnesol is assu med to be a biologically active substance that regulates ion channel activi ty in the glial cell membrane. Depressing rapid changes of the membrane pot ential 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. J. Neurosci. Res. 62:396-402, 2000. (C) 2000 Wiley-Liss, Inc.