The role of the BK channel in potassium homeostasis and flow-induced renal potassium excretion.
The kidney is the major regulator of potassium homeostasis. In addition to the ROMK channels, large conductance Ca(2+)-activated K(+) (BK) channels are expressed in the apical membrane of the aldosterone sensitive distal nephron where they could contribute to renal K(+) secretion. We studied flow-induced K(+) secretion in BK channel alpha-subunit knockout (BK(-/-)) mice by acute pharmacologic blockade of vasopressin V(2) receptors, which caused similar diuresis in wild-type and knockout mice. However, wild-type mice, unlike the BK(-/-), had a concomitant increase in urinary K(+) excretion and a significant correlation between urinary flow rate and K(+) excretion. Both genotypes excreted similar urinary amounts of K(+) irrespective of K(+) diet. This was associated, however, with higher plasma aldosterone and stronger expression of ROMK in the apical membrane of the aldosterone-sensitive portions of the distal nephron in the knockout than in the wild-type under control diet and even more so with the high-K(+) diet. High-K(+) intake significantly increased the renal expression of the BK channel in the wild-type mouse. Finally, despite the higher plasma K(+) and aldosterone levels, BK(-/-) mice restrict urinary K(+) excretion when placed on a low-K(+) diet to the same extent as the wild-type. These studies suggest a role of the BK channel alpha-subunit in flow-induced K(+) secretion and in K(+) homeostasis. Higher aldosterone and an upregulation of ROMK may compensate for the absence of functional BK channels.
Rieg
T
T
Institute of Pharmacology and Toxicology, Medical Faculty of the Eberhard Karls University, Wilhelmstrasse 56, 72074 Tübingen, Germany.
Vallon
V
V
Sausbier
M
M
Sausbier
U
U
Kaissling
B
B
Ruth
P
P
Osswald
H
H
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D005786:Gene Expression Regulation; D005838:Genotype; D006706:Homeostasis; D007668:Kidney / Q000502:physiology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D011188:Potassium / Q000008:administration & dosage / Q000009:adverse effects / Q000652:urine*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D012890:Sleep
D065092:Antidiuretic Hormone Receptor Antagonists; C510693:Kcnj1 protein, mouse; D051036:Large-Conductance Calcium-Activated Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011188:Potassium