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: 294/1/F212    most recent 00244.2007v1 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 Google Scholar Google Scholar Articles by Fellner, S. K. Articles by Arendshorst, W. J. Search for Related Content PubMed PubMed Citation Articles by Fellner, S. K. Articles by Arendshorst, W. J.

Angiotensin II-stimulated Ca²⁺ entry mechanisms in afferent arterioles: role of transient receptor potential canonical channels and reverse Na⁺/Ca²⁺ exchange

Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Submitted 25 May 2007 ; accepted in final form 26 October 2007

In afferent arterioles, the signaling events that lead to an increase in cytosolic Ca²⁺ concentration ([Ca²⁺]_i) and initiation of vascular contraction are increasingly being delineated. We have recently studied angiotensin II (ANG II)-mediated effects on sarcoplasmic reticulum (SR) mobilization of Ca²⁺ and the role of superoxide and cyclic adenosine diphosphoribose in these processes. In the current study we investigated the participation of transient receptor potential canonical channels (TRPC) and a Na⁺/Ca²⁺ exchanger (NCX) in Ca²⁺ entry mechanisms. Afferent arterioles, isolated with the magnetized polystyrene bead method, were loaded with fura-2 to measure [Ca²⁺]_i ratiometrically. We observed that the Ca²⁺-dependent chloride channel blocker niflumic acid (10 and 50 µ M) affects neither the peak nor plateau [Ca²⁺]_i response to ANG II. Arterioles were pretreated with ryanodine (100 µM) and TMB-8 to block SR mobilization via the ryanodine receptor and inositol trisphosphate receptor, respectively. The peak [Ca²⁺]_i response to ANG II was reduced by 40%. Addition of 2-aminoethoxydiphenyl borane to block TRPC-mediated Ca²⁺ entry inhibited the peak [Ca²⁺]_i ANG II response by 80% and the plateau by 74%. Flufenamic acid (FFA; 50 µM), which stimulates TRPC6, caused a sustained increase of [Ca²⁺]_i of 146 nM. This response was unaffected by diltiazem or nifedipine. KB-R7943 (at the low concentration of 10 µM) inhibits reverse (but not forward) mode NCX. KB-R7943 decreased the peak [Ca²⁺]_i response to ANG II by 48% and to FFA by 38%. We conclude that TRPC6 and reverse-mode NCX may be important Ca²⁺ entry pathways in afferent arterioles.

renal microcirculation; voltage-gated calcium entry; vascular smooth muscle cell