Membrane voltage and whole-cell currents in cultured pericytes of control rats and rats with retinal dystrophy.
OBJECTIVE
Retinal vascular changes are associated with retinitis pigmentosa in man and the retinal dystrophy of the Royal College of Surgeons (RCS) rat. Recently we demonstrated that retinal capillary pericytes possess electrical membrane characteristics typical for smooth muscle cells and may thus regulate retinal blood flow in vivo.


METHODS
In the present study we compared cultured pericytes of 5-7 day old RCS and control rats by measurement of membrane voltage (Vmem) with microelectrodes and currents with the whole-cell configuration of the patch-clamp technique.


RESULTS
Resting membrane voltage (-37.6 mV +/- 1.0 mV, n = 106 and -36.6 mV +/- 0.7 mV, n = 102, respectively) and whole-cell currents, which are mainly determined by a potassium conductance, were comparable in pericytes of control and RCS rats. The electrogenic component of the Na(+)-K(+)-ATPase in RCS rat pericytes was reduced, because depolarization of their membrane voltage by Na(+)-K(+)-ATPase inhibitor ouabain (10(-4) mol.1-1 or K+ free solution was significantly decreased compared to control pericytes. Norepinephrine (10(-5) mol.1-1) depolarized Vmem of control rat pericytes by delta 7.0 mV +/- 1.3 mV (n = 7), whereas it hyperpolarized Vmem of RCS rat pericytes by delta 2.0 mV +/- 0.8 mV (n = 11). The depolarization of Vmem by histamine (10(-5) mol.1-1) was significantly reduced in pericytes of RCS rats (delta 2.6 mV +/- 0.4 mV, n = 7) compared to control pericytes (delta 4.3 mV +/- 0.5 mV, n = 6). In pericytes of RCS rats ATP-induced activation of inward and outward currents and depolarization of membrane voltage were also significantly reduced.


CONCLUSIONS
The data indicate that there are differences in the electrophysiological properties of retinal capillary pericytes of 5-7 days old RCS and control rats. Whereas resting membrane voltage and K+ conductance are comparable in both groups, there are significant differences in the electrical activity of Na(+)-K(+)-ATPase and in the effects of vasoactive substances on the membrane voltage and currents. These differences might contribute to the vascular changes observed in RP, and possibly accelerate the progress of retinal dystrophy.
Wagner
U
U
Institut für Klinische Physiologie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Germany.
Wiederholt
M
M
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D016623:Ion Pumps / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D012162:Retinal Degeneration / Q000473:pathology / Q000503:physiopathology*; D012171:Retinal Vessels / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D004791:Enzyme Inhibitors; D016623:Ion Pumps; D010042:Ouabain; D006632:Histamine; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium; D009638:Norepinephrine