Potassium channel contributions to afferent arteriolar tone in normal and diabetic rat kidney.
We previously reported an enhanced tonic dilator impact of ATP-sensitive K+ channels in afferent arterioles of rats with streptozotocin (STZ)-induced diabetes. The present study explored the hypothesis that other types of K+ channel also contribute to afferent arteriolar dilation in STZ rats. The in vitro blood-perfused juxtamedullary nephron technique was utilized to quantify afferent arteriolar lumen diameter responses to K+ channel blockers: 0.1-3.0 mM 4-aminopyridine (4-AP; KV channels), 10-100 microM barium (KIR channels), 1-100 nM tertiapin-Q (TPQ; Kir1.1 and Kir3.x subfamilies of KIR channels), 100 nM apamin (SKCa channels), and 1 mM tetraethylammonium (TEA; BKCa channels). In kidneys from normal rats, 4-AP, TEA, and Ba2+ reduced afferent diameter by 23 +/- 3, 8 +/- 4, and 18 +/- 2%, respectively, at the highest concentrations employed. Neither TPQ nor apamin significantly altered afferent diameter. In arterioles from STZ rats, a constrictor response to TPQ (22 +/- 4% decrease in diameter) emerged, and the response to Ba2+ was exaggerated (28 +/- 5% decrease in diameter). Responses to the other K+ channel blockers were similar to those observed in normal rats. Moreover, exposure to either TPQ or Ba2+ reversed the afferent arteriolar dilation characteristic of STZ rats. Acute surgical papillectomy did not alter the response to TPQ in arterioles from normal or STZ rats. We conclude that 1) KV, KIR, and BKCa channels tonically influence normal afferent arteriolar tone, 2) KIR channels (including Kir1.1 and/or Kir3.x) contribute to the afferent arteriolar dilation during diabetes, and 3) the dilator impact of Kir1.1/Kir3.x channels during diabetes is independent of solute delivery to the macula densa.
Troncoso Brindeiro
Carmen M
CM
Department of Cellular and Integrative Physiology, University of Nebraska College of Medicine, Omaha, NE, USA.
Fallet
Rachel W
RW
Lane
Pascale H
PH
Carmines
Pamela K
PK
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D001514:Bee Venoms / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019789:Tetraethylammonium / Q000494:pharmacology
D001514:Bee Venoms; D015221:Potassium Channels; D001030:Apamin; C029738:tertiapin; D019789:Tetraethylammonium; D015761:4-Aminopyridine