Regulation of Na channels in the rat cortical collecting tubule: effects of cAMP and methyl donors.
The whole cell patch-clamp technique was used to investigate the interactions of the amiloride-sensitive Na channel of the rat cortical collecting tubule (CCT) with adenosine 3',5'-cyclic monophosphate (cAMP) and with methyl donors. The amiloride-sensitive whole cell current (INa) was measured in principal cells of dissected, split-open tubules from rats maintained either on a control diet or on a low-Na diet to increase endogenous aldosterone secretion. With Na-depleted animals, INa was highest immediately after rupture of the membrane patch and averaged 325 pA at a membrane potential of -60 mV. INa declined over 15 min to approximately 35% of the initial value. With 8-(4-chlorophenylthio)-cAMP in the pipette, INa increased within 5 min of membrane rupture and was maintained for 15 min at levels three- to fourfold higher than the corresponding control values. With Na-replete animals, INa was undetectable (< 10 pA) without cAMP. With cAMP in the pipette, INa averaged 40 pA. In cell-attached patches on tubules from Na-replete rats exposed to cAMP, single Na channels were observed with conductive and kinetic properties similar to those from Na-depleted rats but at lower density. Inclusion of the methyl donor S-adenosyl methionine to the pipette solution did not increase INa in CCTs from Na-replete rats, either in the presence or absence of cAMP. The methylation inhibitor S-adenosyl homocysteine did not affect INa in CCT from Na-depleted animals.
Frindt
G
G
Department of Physiology and Biophysics, Cornell University Medical College, New York, New York 10021, USA.
Palmer
L G
LG
D000450:Aldosterone / Q000378:metabolism; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology*; D004039:Diet, Sodium-Restricted; D004553:Electric Conductivity; D005260:Female; D007672:Kidney Cortex; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D008297:Male; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012436:S-Adenosylmethionine / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D013873:Thionucleotides / Q000494:pharmacology
D015222:Sodium Channels; D013873:Thionucleotides; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D000450:Aldosterone; D000584:Amiloride; D012436:S-Adenosylmethionine; D000242:Cyclic AMP