Expression and function of native potassium channel (Kvα1) 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 fur 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 nut 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, nut 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.