Age- and disease-related changes of calcium channel-mediated currents in human Muller glial cells

PURPOSE. To determine whether the expression of voltage-gated Ca2+ channels in human Muller glial cells changes during normal aging and in cells from patients with proliferative vitreoretinopathy (PVR). METHODS. Muller cells were enzymatically isolated from retinas of healthy d onors and from excised retinal pieces of patients with PVR, and the whole-c ell, voltage-clamp technique was used to characterize the current densities of transient, low-voltage-activated calcium channels and of sustained, hig h-voltage-activated calcium channels, respectively. To obtain maximal curre nts through both channel types, Na+ ions were used as the charge carrier. RESULTS. During normal aging, Muller cells developed a hypertrophy, as indi cated by an increase of the cell membrane capacitance. The mean membrane ca pacitance of cells from aged donors (greater than or equal to 60 years old) was elevated by 25% compared with cells from younger donors. The hypertrop hy was not accompanied by a changed density of low-voltage-activated curren ts, whereas the density of the high-voltage-activated currents was enhanced by 76%. The density of the high-voltage-activated currents increased in co rrelation with the increase of the cell membrane capacitance and with the a ge of the donors. In the case of PVR, Muller cells displayed a strong hyper trophy accompanied by a downregulation of both current types by approximate ly 65%. CONCLUSIONS. Both normal aging and PVR cause a gliotic reactivity of human Muller cells, as indicated by their hypertrophy. The type of reactivity, ho wever, differs between the two conditions. Normal aging is accompanied by a n increased expression of voltage-gated Ca2+ channels, whereas in PVR Ca2channel expression is decreased.