TASK channels are not required to mount an aldosterone secretory response to metabolic acidosis in mice.
The stimulation of aldosterone production by acidosis enhances proton excretion and serves to limit disturbances in systemic acid-base equilibrium. Yet, the mechanisms by which protons stimulate aldosterone production from cells of the adrenal cortex remain largely unknown. TWIK-related acid sensitive K channels (TASK) are inhibited by extracellular protons within the physiological range and have emerged as important regulators of aldosterone production in the adrenal cortex. Here we show that congenic C57BL/6J mice with genetic deletion of TASK-1 (K(2P)3.1) and TASK-3 (K(2P)9.1) channel subunits overproduce aldosterone and display an enhanced sensitivity to steroidogenic stimuli, including a more pronounced steroidogenic response to chronic NH(4)Cl loading. Thus, we conclude that TASK channels are not required for the stimulation of aldosterone production by protons but their inhibition by physiological acidosis may contribute to full expression of the steroidogenic response.
University of Virginia, Department of Pharmacology, 1340 Jefferson Park Ave., Charlottesville, VA 22908, USA. Nag4g@virginia.edu
Nick A
NA
Guagliardo
Junlan
J
Yao
Douglas A
DA
Bayliss
Paula Q
PQ
Barrett
D000136:Acid-Base Equilibrium / Q000187:drug effects; D000138:Acidosis / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology / Q000652:urine; D000143:Acids / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism* / Q000652:urine; D000643:Ammonium Chloride / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D004573:Electrolytes / Q000097:blood / Q000652:urine; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism*; D015221:Potassium Channels / Q000172:deficiency / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain / Q000172:deficiency / Q000378:metabolism*; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012083:Renin / Q000097:blood
D000143:Acids; D004573:Electrolytes; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D044140:Receptor, Angiotensin, Type 1; C511784:TASK3 protein, mouse; D000643:Ammonium Chloride; C420132:potassium channel subfamily K member 3; D000450:Aldosterone; D012083:Renin