KATP channel conductance of descending vasa recta pericytes

Using nystatin-perforated patch-clamp and whole cell recording, we tested the hypothesis that K-ATP channels contribute to resting conductance of rat descending vasa recta (DVR) pericytes and are modulated by vasoconstrictors. The K-ATP blocker glybenclamide (Glb; 10 mu M) depolarized pericytes and inhibited outward currents of cells held at -40 mV. K-ATP openers pinacidil (Pnc; 10 mu M) and P-1075 (1 mu M) hyperpolarized pericytes and transiently augmented outward currents. All effects of Pnc and P-1075 were fully reversed by Glb. Inward currents of pericytes held at -60 mV in symmetrical 140 mM K+ were markedly augmented by Pnc and fully reversed by Glb. Ramp depolarizations in symmetrical K+, performed in Pnc and Pnc + Glb, yielded a Pnc-induced, Glb-sensitive K-ATP difference current that lacked rectification and reversed at 0 mV. Immunostaining identified both K(IR)6.1, K(IR)6.2 inward rectifier subunits and sulfonurea receptor subtype 2B. ANG II ( 1 and 10 nM) and endothelin-1 ( 10 nM) but not vasopressin (100 nM) significantly lowered holding current at -40 mV and abolished Pnc-stimulated outward currents. We conclude that DVR pericytes express K-ATP channels that make a significant contribution to basal K+ conductance and are inhibited by ANG II and endothelin-1.