Expression and function of native potassium channel [K(V)alpha1] subunits in terminal arterioles of rabbit.
1. In this study we investigated the expression and function of the K(V)alpha1 subfamily of voltage-gated K(+) channels in terminal arterioles from rabbit cerebral circulation. 2. K(+) current was measured from smooth muscle cells within intact freshly isolated arteriolar fragments. Current activated on depolarisation positive of about -45 mV and a large fraction of this current was blocked by 3,4-diaminopyridine (3,4-DAP) or 4-aminopyridine (4-AP), inhibitors of K(V) channels. Expression of cRNA encoding K(V)1.6 in Xenopus oocytes also generated a 4-AP-sensitive K(+) current with a threshold for activation near -45 mV. 3. Immunofluorescence labelling revealed K(V)1.2 to be specifically localised to endothelial cells, and K(V)1.5 and K(V)1.6 to plasma membranes of smooth muscle cells. 4. K(V) channel current in arteriolar fragments was blocked by correolide (which is specific for the K(V)alpha1 family of K(V) channels) but was resistant to recombinant agitoxin-2 (rAgTX2; which inhibits K(V)1.6 but not K(V)1.5). Heterologously expressed K(V)2.1 was resistant to correolide, and K(V)1.6 was blocked by rAgTX2. 5. Arterioles that were mildly preconstricted and depolarised by 0.1-0.3 nM endothelin-1 constricted further in response to 3,4-DAP, 4-AP or correolide, but not to rAgTX2. 6. We suggest that K(V)alpha1 channels are expressed in smooth muscle cells of terminal arterioles, underlie a major part of the voltage-dependent K(+) current, and have a physiological function to oppose vasoconstriction. K(V)alpha1 complexes without K(V)1.5 appear to be uncommon.
Cheong
A
A
School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UK.
Dedman
A M
AM
Beech
D J
DJ
D015761:4-Aminopyridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077770:Amifampridine; D000818:Animals; D001160:Arterioles / Q000166:cytology / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002560:Cerebrovascular Circulation; D051668:Delayed Rectifier Potassium Channels; D004553:Electric Conductivity; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D051663:Kv1.2 Potassium Channel; D051666:Kv1.5 Potassium Channel; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D009865:Oocytes; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism* / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D011817:Rabbits; D012604:Scorpion Venoms / Q000494:pharmacology; D014018:Tissue Distribution; D014315:Triterpenes / Q000494:pharmacology; D014982:Xenopus laevis
D051668:Delayed Rectifier Potassium Channels; D051663:Kv1.2 Potassium Channel; D051666:Kv1.5 Potassium Channel; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012604:Scorpion Venoms; D014315:Triterpenes; C118657:correolide; C087603:agitoxin 2; D015761:4-Aminopyridine; D000077770:Amifampridine