Inward Rectifier K+ Currents and Kir2.1 Expression in Renal Afferent and Efferent Arterioles

Abstract

The afferent and efferent arterioles regulate the inflow and outflow resistance of the glomerulus, acting in concert to control the glomerular capillary pressure and glomerular filtration rate. The myocytes of these two vessels are remarkably different, especially regarding electromechanical coupling. This study investigated the expression and function of inward rectifier K ϩ channels in these two vessels using perfused hydronephrotic rat kidneys and arterioles and myocytes isolated from normal rat kidneys. In afferent arterioles pre-constricted with angiotensin II, elevating [K ϩ ] 0 from 5 to 15 mmol/L induced hyperpolarization (Ϫ27 Ϯ 2 to Ϫ41 Ϯ 3 mV) and vasodilation (6.6 Ϯ 0.9 to 13.1 Ϯ 0.6 m). This manipulation also attenuated angiotensin II-induced Ca 2ϩ signaling, an effect blocked by 100 mol/L Ba 2ϩ . By contrast, elevating [K ϩ ] 0 did not alter angiotensin II-induced Ca 2ϩ signaling or vasoconstriction in efferent arterioles, even though a significant hyperpolarization was observed (from Ϫ30 Ϯ 1 to Ϫ37 Ϯ 3 mV, P ϭ 0.003). Both vessels expressed mRNA for Kir2.1 and exhibited anti-Kir2.1 antibody labeling. Patch-clamp measurements revealed prominent inwardly rectifying and Ba 2ϩ -sensitive currents in afferent and efferent arteriolar myocytes. Our findings indicate that both arterioles express an inward rectifier K ϩ current, but that modulation of this current alters responsiveness of only the afferent arteriole. The expression of Kir in the efferent arteriole, a resistance vessel whose tone is not affected by membrane potential, is intriguing and may suggest a novel function of this channel in the renal microcirculation.

Closure of multiple types of K+ channels is necessary to induce changes in renal vascular resistance in vivo in rats

“…In the blood-perfused juxtamedullary nephron preparation TEA or Ba 2+ reduced rat afferent arteriolar diameter by 8 to 23% [49]. A role for K ir channels has been proposed in the regulation of the afferent arteriolar tone in the rat hydronephrotic kidney [4,5].…”

“…Effects of a cocktail of K + channel inhibitors on afferent arteriolar diameter K + channels (K ir , K ATP and BK Ca [4,7,40]) have been shown to not only influence afferent diameter but also efferent diameter. Therefore, we wished to examine the direct effect of K + channel inhibitors on the afferent arteriole diameter.…”

“…The resting membrane potential of afferent arteriolar VSMC is approximately −55 to −40 mV [1,5], which is close to the threshold voltage for L-type Ca 2+ channels, and small changes in K + channel activity could, therefore, change afferent arteriolar VSMC membrane potential [4,5] and RVR. K + channels (K ir , K ATP and BK Ca [4,7,40]) have also been shown to influence efferent arteriolar diameter where the membrane potential is also approximately −40 mV [28].…”

“…K + channels (K ir , K ATP and BK Ca [4,7,40]) have also been shown to influence efferent arteriolar diameter where the membrane potential is also approximately −40 mV [28].…”

A Multicellular Vascular Model of the Renal Myogenic Response

“…Throughout this study, we consider an afferent arteriole of total length L AA = 60 µm that consists of cells with axial length h = 3 µm approximately of the same dimensions as reported in [69,70]. Based on the estimated L AA and h, the model afferent arteriole is discretized into N AA = 20 cells.…”