SPERMINE SPERMIDINE IS EXPRESSED BY RETINAL GLIAL (MULLER) CELLS AND CONTROLS DISTINCT K+ CHANNELS OF THEIR MEMBRANE/

There is recent evidence that polyamines such as spermine (spm) and sp ermidine (spd) may act as endogenous modulators of the activity of inw ardly rectifying K+ channels. This type of K+ channels is abundantly e xpressed by retinal glial (Muller) cells where they are involved in im portant glial cell functions such as the clearance of excess extracell ular Kf ions. This prompted us to study the following questions, i) do mammalian Muller cells contain endogenous spm/spd?; ii) do Muller cel ls possess the enzymes (e.g., ornithine decarboxylase, ODC) necessary to produce spm/spd?; and iii) does application of exogenous spm/spd ex ert specific effects onto inwardly rectifying K+ channels of Muller ce lls? Immunocytochemical studies were performed on histological section s of guinea-pig, rabbit, porcine, and human retinae, and on enzymatica lly dissociated Muller cells. Whole-cell and patch-clamp recordings we re performed on enzymatically dissociated porcine and guinea-pig Mulle r cells. All above-mentioned questions could be answered with ''yes.'' Specifically, the majority of Muller cells were labeled with antibodi es directed to spm/spd, both within retinal sections and enzymatically isolated from retinal tissue. Muller cells in normal retinae express low levels of ODC but increase this expression markedly in cases of re tinal pathology such as experimental epiretinal melanoma. Externally a pplied polyamines (1 mM) reduce (predominantly inward) whole-cell K+ c urrents, with the efficiacies being spm > spd > put. If applied at the inside of membrane patches, spm (1 mM) blocks completely the outward currents through inwardly rectifying K+ channels but fails to affect t he activity of large conductance, Ca2+-activated K+ channels. It is co ncluded that Muller cells contain endogenous channel-active polyamines , the synthesis of which may be up-regulated in pathological situation s, and which may be involved in the control of both glial function and cell proliferation. (C) 1998 Wiley-Liss, Inc.