HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/1/F227    most recent 00057.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Liu, W. Articles by Satlin, L. M. Search for Related Content PubMed PubMed Citation Articles by Liu, W. Articles by Satlin, L. M.

Ca²⁺ dependence of flow-stimulated K secretion in the mammalian cortical collecting duct

¹Division of Pediatric Nephrology, Department of Pediatrics, Mount Sinai School of Medicine, New York, New York; and ²Renal Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania

Submitted 6 February 2007 ; accepted in final form 25 March 2007

Apical low-conductance SK and high-conductance Ca²⁺-activated BK channels are present in distal nephron, including the cortical collecting duct (CCD). Flow-stimulated net K secretion (J_K) in the CCD is 1) blocked by iberiotoxin, an inhibitor of BK but not SK channels, and 2) associated with an increase in [Ca²⁺]_i, leading us to conclude that BK channels mediate flow-stimulated J_K. To examine the Ca²⁺ dependence and sources of Ca²⁺ contributing to flow-stimulated J_K, J_K and net Na absorption (J_Na) were measured at slow (1) and fast (5 nl·min^–1·mm^–1) flow rates in rabbit CCDs microperfused in the absence of luminal Ca²⁺ or after pretreatment with BAPTA-AM to chelate intracellular Ca²⁺, 2-aminoethoxydiphenyl borate (2-APB), to inhibit the inositol 1,4,5-trisphosphate (IP₃) receptor or thapsigargin to deplete internal stores. These treatments, which do not affect flow-stimulated J_Na (Morimoto et al. Am J Physiol Renal Physiol 291: F663–F669, 2006), inhibited flow-stimulated J_K. Increases in [Ca²⁺]_i stimulate exocytosis. To test whether flow induces exocytic insertion of preformed BK channels into the apical membrane, CCDs were pretreated with 10 µM colchicine (COL) to disrupt microtubule function or 5 µg/ml brefeldin-A (BFA) to inhibit delivery of channels from the intracellular pool to the plasma membrane. Both agents inhibited flow-stimulated J_K but not J_Na (Morimoto et al. Am J Physiol Renal Physiol 291: F663–F669, 2006), although COL but not BFA also blocked the flow-induced [Ca²⁺]_i transient. We thus speculate that BK channel-mediated, flow-stimulated J_K requires an increase in [Ca²⁺]_i due, in part, to luminal Ca²⁺ entry and ER Ca²⁺ release, microtubule integrity, and exocytic insertion of preformed channels into the apical membrane.

maxi-K channel; BK channel; SK channel; mechanoregulation; ENaC

This article has been cited by other articles:

				M. R. Quinlan, N. G. Docherty, R. W. G. Watson, and J. M. Fitzpatrick Exploring mechanisms involved in renal tubular sensing of mechanical stretch following ureteric obstruction Am J Physiol Renal Physiol, July 1, 2008; 295(1): F1 - F11. [Abstract] [Full Text] [PDF]

				L. Galizia, M. P. Flamenco, V. Rivarola, C. Capurro, and P. Ford Role of AQP2 in activation of calcium entry by hypotonicity: implications in cell volume regulation Am J Physiol Renal Physiol, March 1, 2008; 294(3): F582 - F590. [Abstract] [Full Text] [PDF]