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Potassium channel contributions to afferent arteriolar tone in normal and diabetic rat kidney

¹Department of Cellular and Integrative Physiology and ²Department of Pediatrics, University of Nebraska College of Medicine, Omaha, Nebraska

Submitted 26 November 2007 ; accepted in final form 15 May 2008

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; K_V channels), 10–100 µM barium (K_IR channels), 1–100 nM tertiapin-Q (TPQ; Kir1.1 and Kir3.x subfamilies of K_IR channels), 100 nM apamin (SK_Ca channels), and 1 mM tetraethylammonium (TEA; BK_Ca 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) K_V, K_IR, and BK_Ca channels tonically influence normal afferent arteriolar tone, 2) K_IR 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.

tertiapin-Q; barium; TEA; apamin; 4-aminopyridine

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