Kv1 and Kir2 potassium channels are expressed in rat brain endothelial cells.
The endothelial cells of the brain microvasculature, which constitute the blood-brain barrier, secrete K+ into brain interstitial fluid. K+ channels are predicted to have a central role to play in this process. The aim of the following study was to characterise K+ channels in primary cultures of endothelial cells isolated from rat brain microvessels by whole-cell patch clamp and real-time polymerase chain reaction. In the 4 h after plating, the rat brain endothelial cells expressed predominantly a depolarisation-activated delayed-rectifying outward K+ conductance and a time-independent inwardly rectifying K+ conductance prominent at hyperpolarising potentials. The outward current was inhibited by 1 mM 4-aminopyridine (4AP), 10 nM margatoxin and 100 nM dendrotoxin-K, indicating the involvement of Kv1 channels. The half maximal activation voltage and time constants of activation and inactivation of the 4AP-sensitive current were similar to Kv1.3. The inwardly rectifying conductance was inhibited by Ba2+ in a dose- and voltage-dependent fashion; the kinetics of which resembled Kir2 channels. Quantification of messenger ribonucleic acid transcripts revealed Kv1.3>1.2=1.4=1.5=1.6 and Kir2.1=2>2.3. In current-clamp experiments, both 4AP and Ba2+ depolarised the membrane potential. In conclusion, rat brain endothelial cells express Kv1 and Kir2 K+ channels, both of which participate in setting membrane potential and could mediate K+ secretion into the brain interstitial fluid.
Millar
Ian D
ID
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK.
Wang
Shanshan
S
Brown
Peter D
PD
Barrand
Margery A
MA
Hladky
Stephen B
SB
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000098:blood supply*; D002831:Choroid Plexus / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D051664:Kv1.3 Potassium Channel / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012604:Scorpion Venoms / Q000494:pharmacology
C489461:Kir2.1 channel; C489463:Kir2.2 channel; D051664:Kv1.3 Potassium Channel; D010455:Peptides; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D012604:Scorpion Venoms; C081506:dendrotoxin K; D001464:Barium; C077910:margatoxin; D015761:4-Aminopyridine; D011188:Potassium