Membrane conductance of Müller glial cells in proliferative diabetic retinopathy.
BACKGROUND
It is not known whether the membrane features of human Müller cells are altered in proliferative diabetic retinopathy (PDR). We performed a study to investigate the expression of several distinct forms of membrane conductance in Müller glial cells from a patient with PDR compared to cells from healthy donors (control cells).


METHODS
Müller cells were isolated 2 hours after vitreoretinal surgery in the case of the patient and within 24 hours in the case of the autopsy eyes. Whole-cell voltage-clamp recordings were made. The results for the two groups were compared with the Mann-Whitney U test.


RESULTS
As assayed by the whole-cell membrane capacitance, the cells from the patient with PDR showed hypertrophy in comparison to the control cells (mean 85.1 pF [standard deviation (SD) 19.7 pF] vs. 54.3 pF [SD 13.8 pF]). The cells from the patient displayed strong downregulation of inwardly rectifying potassium ion (Kir) currents (mean 0.41 [SD 0.24] pA/pF, compared to 3.43 [SD 1.86] pA/pF for the control cells). The Kir current downregulation was accompanied by a less negative membrane potential (-57.3 mV [SD 16.9 mV], compared with -82.3 mV [SD 5.3 mV] for the control cells). Both the number and the amplitude of voltage-gated sodium ion currents were enhanced in cells from the patient. When P2X7 receptors were activated by 2'-/3'-O-(4-benzoylbenzoyl)-adenosine triphosphate, cells in both groups displayed opening of a cation conductance and, simultaneously, an increase in currents through calcium ion-activated potassium ion channels.


CONCLUSIONS
Changes in Müller cell membrane conductance in PDR are similar to those described in proliferative vitreoretinopathy. The down-regulation of active Kir channels and the membrane depolarization likely disturb voltage-dependent Müller cell functions, such as regulation of local ion concentrations and uptake of neurotransmitters. The enhanced entry of calcium ions from the extracellular space and the subsequent stimulation of calcium-activated potassium channels support Müller cell proliferation in PDR.
Bringmann
Andreas
A
Department of Neurophysiology, Paul Flechsig Institute of Brain Research, University of Leipzig, Germany. bria@medizin.uni-leipzig.de
Pannicke
Thomas
T
Uhlmann
Susanne
S
Kohen
Leon
L
Wiedemann
Peter
P
Reichenbach
Andreas
A
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000368:Aged; D002118:Calcium / Q000502:physiology; D002412:Cations / Q000378:metabolism; D002462:Cell Membrane / Q000502:physiology; D015536:Down-Regulation; D025802:Electric Capacitance; D004553:Electric Conductivity; D006801:Humans; D006984:Hypertrophy; D008564:Membrane Potentials; D009457:Neuroglia / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology; D058486:Receptors, Purinergic P2X7; D012016:Reference Values; D012160:Retina / Q000473:pathology / Q000503:physiopathology*; D015222:Sodium Channels / Q000502:physiology; D018630:Vitreoretinopathy, Proliferative / Q000503:physiopathology*
D002412:Cations; C546468:P2RX7 protein, human; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D015222:Sodium Channels; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D000255:Adenosine Triphosphate; D002118:Calcium