Abstract
BK channels are expressed in intercalated cells (ICs) and principal cells (PCs) in the cortical collecting duct (CCD) of the mammalian kidney and have been proposed to be responsible for flow-induced K+ secretion (FIKS) and K+ adaptation. To examine the IC-specific role of BK channels, we generated a mouse with targeted disruption of the pore-forming BK α subunit (BKα) in ICs (IC-BKα-KO). Whole cell charybdotoxin-sensitive (ChTX-sensitive) K+ currents were readily detected in control ICs but largely absent in ICs of IC-BKα-KO mice. When placed on a high K+ (HK) diet for 13 days, blood [K+] was significantly greater in IC-BKα-KO mice versus controls in males only, although urinary K+ excretion rates following isotonic volume expansion were similar in males and females. FIKS was present in microperfused CCDs isolated from controls but was absent in IC-BKα-KO CCDs of both sexes. Also, flow-stimulated epithelial Na+ channel-mediated (ENaC-mediated) Na+ absorption was greater in CCDs from female IC-BKα-KO mice than in CCDs from males. Our results confirm a critical role of IC BK channels in FIKS. Sex contributes to the capacity for adaptation to a HK diet in IC-BKα-KO mice.
Highlights
Urinary K+ secretion in the aldosterone-sensitive distal nephron (ASDN), including the late distal convoluted tubule (DCT), connecting tubule (CNT), and cortical collecting duct (CCD), is mediated by at least 2 K+ secretory channels: a low-conductance renal outer medullary potassium (ROMK) channel [1,2,3,4,5] and a high-conductance Ca2+, voltage, and stretch-activated BK channel [2, 6,7,8,9,10,11,12,13]
intercalated cells (ICs) represent less than 30% of the cells present in the CCD and a very small subset of cells present in the cortex of the mouse kidney, and BK channels are present in both principal cells (PCs) and ICs of the CCD [24]
This study aimed to examine the contribution of the IC BK channel to the renal adaptation to dietary K+ loading and flow-induced K+ secretion (FIKS) in the setting of a high K+ (HK) diet
Summary
Urinary K+ secretion in the aldosterone-sensitive distal nephron (ASDN), including the late distal convoluted tubule (DCT), connecting tubule (CNT), and cortical collecting duct (CCD), is mediated by at least 2 K+ secretory channels: a low-conductance renal outer medullary potassium (ROMK) channel [1,2,3,4,5] and a high-conductance Ca2+-, voltage-, and stretch-activated BK channel [2, 6,7,8,9,10,11,12,13]. Cumulative evidence suggests that the ROMK channel mediates constitutive K+ secretion, while the iberiotoxin-sensitive BK channel, composed of pore-forming α subunits (encoded by Slo or Kcnma1) and accessory β and γ subunits [14,15,16], is responsible for flow-induced K+ secretion (FIKS) [13, 17,18,19,20,21] Both ROMK and BK channels play major roles in the renal adaptation to dietary K+ [17, 20, 22,23,24]. B-type ICs secrete HCO3– via the apical Cl–/HCO3– exchanger pendrin and possess a basolateral H+-ATPase, whereas A-type ICs secrete H+ via an apical H+-ATPase and a basolateral Cl–/HCO3– exchanger similar to the red cell anion exchanger 1 (AE1) [25]
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