Angiotensin II, vasopressin and GTP[gamma-S] inhibit inward-rectifying K+ channels in porcine cerebral capillary endothelial cells.
Cerebral capillaries from porcine brain were isolated, and endothelial cells were grown in primary culture. The whole-cell tight seal patch-clamp method was applied to freshly isolated single endothelial cells, and cells which were held in culture up to one week. With high K+ solution in the patch pipette and in the bath we observed inward-rectifying K+ currents, showing a time-dependent decay in part of the experiments. Ba2+ (1-10 mM) in the bath blocked this current, whereas outside tetraethylammonium (10 mM) decreased the peak current but increased the steady-state current. Addition of 1 microM of angiotensin II or of arginine-vasopressin to the extracellular side caused a time-dependent inhibition of the inward-rectifying K+ current in part of the experiments. Addition of 100 microM GTP[gamma-S] to the patch pipette blocked the K+ inward rectifier. In cell-attached membrane patches two types of single inward-rectifying K+ channels were observed, with single channel conductances of 7 and 35 pS. Cell-attached patches were also obtained at the antiluminal membrane of intact isolated cerebral capillaries. Only one type of K+ channel with g = 30 pS was recorded. In conclusion, inwardly rectifying K+ channels, which can be inhibited by extracellular angiotensin II and arginine-vasopressin, are present in cerebral capillary endothelial cells. The inhibition of this K+ conductance by GTP[gamma-S] indicates that G-proteins are involved in channel regulation. It is suggested that angiotensin II and vasopressin regulate K+ transport across the blood-brain barrier, mediating their effects via G-proteins.
Hoyer
J
J
Max-Planck-Institut für Biophysik, Frankfurt/Main, Federal Republic of Germany.
Popp
R
R
Meyer
J
J
Galla
H J
HJ
Gögelein
H
H
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply*; D001923:Brain Chemistry; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D013552:Swine; D014667:Vasopressins / Q000494:pharmacology*
D015221:Potassium Channels; D014667:Vasopressins; D000804:Angiotensin II; D016244:Guanosine 5'-O-(3-Thiotriphosphate)