Electrophysiological properties of rat retinal Müller (glial) cells in postnatally developing and in pathologically altered retinae

Abstract

Retinal glial Müller cells are characterized by dominant K(+) conductances. The cells may undergo changes of their membrane currents during ontogeny and gliosis as described in rabbit and man. Although the rat retina is often used in physiological experiments, the electrophysiology of rat Müller cells is less well studied. The aim of the present study was to characterize their membrane currents in postnatal development and in two models of retinal degeneration. Freshly isolated cells were subjected to whole-cell patch clamp recordings. During the first 4 weeks after birth of rats, their Müller cells displayed an increase in all membrane currents, particularly in the inward currents elicited at hyperpolarizing potentials. The decrease of the membrane resistance from more than 760 MOmega to less than 50 MOmega was accompanied by a shift of the zero current potential from about -20 mV to -80 mV, similar as earlier observed in developing rabbit Müller cells. These developmental changes were found in pigmented Brown Norway rats as well as in rats with inherited retinal dystrophy (RCS rats). Moreover, an infection of Lewis rats with the Borna disease virus caused substantial neuroretinal degeneration but did not result in a strong reduction of inward currents and of the zero current potential of the Müller cells. Thus, rat Müller cells fail to change their basic membrane properties in two different models of retinal pathology. This is in contrast to human and rabbit Müller cells, which have been shown to undergo dramatic changes of their membrane physiology in response to retinal diseases and injuries.

Altered membrane physiology in Müller glial cells after transient ischemia of the rat retina

“…5H). This pharmacological profile is very similar to earlier data from rat Mü ller cells (Felmy et al, 2001;Pannicke et al, 2001). …”

“…Cells from untreated rats did not display fast inactivating A-type K ϩ currents (n ϭ 16; Fig. 5E), as previously shown in Mü ller cells of Brown-Norway rats (Felmy et al, 2001). However, after retinal ischemia, the cells rapidly upregulated their expression of A-type K ϩ currents (Fig.…”

“…The I-V relations of the whole-cell currents (Fig. 2B) reveal very weak inward rectification of the K ϩ currents near the zero-current potential, as previously described to be typical for retinal glial cells of the rat (Felmy et al, 2001) and for currents mediated by the Kir4.1 channel (Shuck et al, 1997), known to be the predominant Kir channel subtype expressed by retinal glial cells (Ishii Fig. 1.…”

Early remodeling of müller cells in the rd/rd mouse model of retinal dystrophy

“…In the rd/rd retina, we saw no significant changes in Müller cell membrane potential or K þ conductance compared to normal mice during active photoreceptor degeneration. Other animal models of retinal degeneration including the Royal College of Surgeons (RCS) rat and the rds mouse also maintain normal Müller cell electrophysiology during retinal degeneration (Kacza et al, 2001;Felmy et al, 2001;Iandiev et al, 2006;Bolz et al, 2008). Maintenance of normal electrophysiology and the absence of Müller cell proliferation are highly indicative of conservative reactive gliosis in the rd/rd retina during stages of active photoreceptor degeneration.…”

“…Glial cell reactivity, or gliosis, is universal to retinal disease . Müller cells, the major glial cells in the retina, become reactive during the early stages of degeneration (Ekstr€ om et al, 1988;Felmy et al, 2001;Iandiev et al, 2006) then contribute to the development of a glial seal that envelops the entire retina at late-stage degeneration (Jones et al, , 2005(Jones et al, , 2006Marc et al, 2008). The ability to prevent or restore vision by gene therapy, stem cell transplantation, or prosthetic devices depends on the ability to overcome these glial cell modifications (Farrar et al, 2002;Dejneka et al, 2003;MacLaren et al, 2006;Bainbridge et al, 2008).…”