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) Services Email this article to a friend Similar articles in this journal 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 Google Scholar Google Scholar Articles by Piper, A. S. Articles by Large, W. A. Search for Related Content PubMed PubMed Citation Articles by Piper, A. S. Articles by Large, W. A.

Dual effect of blocking agents on Ca²⁺-activated Cl^- currents in rabbit pulmonary artery smooth muscle cells

A. S. Piper, I. A. Greenwood and W. A. Large

The effects of the Cl^- channel antagonists, niflumic acid (NFA), dichloro-diphenylamine 2-carboxylic acid (DCDPC) and diisothiocyanato-stilbene-2,2'-disulphonic acid (DIDS) on Ca²⁺-activated Cl^- current (I_Cl(Ca)) evoked by adding fixed intracellular calcium concentrations ([Ca²⁺]_i) to the pipette solution were studied in rabbit pulmonary artery myocytes. With 250 and 500 nM [Ca²⁺]_i bath application of NFA (100 µM) increased inward current at negative potentials, but inhibited outward current at positive potentials. On wash out of NFA, I_Cl(Ca) was greatly enhanced at all potentials. When external Na⁺ ions were replaced by N-methyl-D-glucamine (NMDG⁺) NFA still enhanced I_Cl(Ca) at negative potentials but the increase of I_Cl(Ca) on wash out was blocked. When the mean reversal potential (E_r) of I_Cl(Ca) was shifted to negative potentials by replacing external Cl^- with SCN^-, NFA increased inward current but blocked outward current suggesting that the effect of NFA is dependent on current flow. Inclusion of NFA in the pipette solution had no effect on I_Cl(Ca). Voltage jump experiments indicated that I_Cl(Ca) displayed characteristic outward current relaxations at +70 mV and inward current relaxations at -80 mV that were abolished by NFA. DCDPC (100 µM) produced similar effects to NFA but 1 mM DIDS produced inhibition of I_Cl(Ca) at both positive and negative potentials and there was no increase in current on wash out of DIDS. These results suggest that NFA and DCDPC, but not DIDS, simultaneously enhance and block I_Cl(Ca) by binding to an external site, probably close to the mouth of the chloride channel.

This article has been cited by other articles:

				S. K. Fellner and W. J. Arendshorst Angiotensin II-stimulated Ca2+ entry mechanisms in afferent arterioles: role of transient receptor potential canonical channels and reverse Na+/Ca2+ exchange Am J Physiol Renal Physiol, January 1, 2008; 294(1): F212 - F219. [Abstract] [Full Text] [PDF]

				S. N. Saleh, J. E. Angermann, W. R. Sones, N. Leblanc, and I. A. Greenwood Stimulation of Ca2+-Gated Cl- Currents by the Calcium-Dependent K+ Channel Modulators NS1619 [1,3-Dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one] and Isopimaric Acid J. Pharmacol. Exp. Ther., June 1, 2007; 321(3): 1075 - 1084. [Abstract] [Full Text] [PDF]

				I. Greenwood, N. Leblanc, and W. Sones Investigation of the differential effects of niflumic acid on Cl currents in vascular myocytes FASEB J, April 1, 2007; 21(5): A521 - A521.

				J. E. Angermann, A. R. Sanguinetti, J. L. Kenyon, N. Leblanc, and I. A. Greenwood Mechanism of the Inhibition of Ca2+-Activated Cl- Currents by Phosphorylation in Pulmonary Arterial Smooth Muscle Cells J. Gen. Physiol., June 26, 2006; 128(1): 73 - 87. [Abstract] [Full Text] [PDF]

				A. Zholos, B. Beck, V. Sydorenko, L. Lemonnier, P. Bordat, N. Prevarskaya, and R. Skryma Ca2+- and Volume-sensitive Chloride Currents Are Differentially Regulated by Agonists and Store-operated Ca2+ Entry J. Gen. Physiol., January 31, 2005; 125(2): 197 - 211. [Abstract] [Full Text] [PDF]

				J. Ledoux, I. A. Greenwood, and N. Leblanc Dynamics of Ca2+-Dependent Cl- Channel Modulation by Niflumic Acid in Rabbit Coronary Arterial Myocytes Mol. Pharmacol., January 1, 2005; 67(1): 163 - 173. [Abstract] [Full Text] [PDF]

				S. N. Saleh and I. A. Greenwood Activation of chloride currents in murine portal vein smooth muscle cells by membrane depolarization involves intracellular calcium release Am J Physiol Cell Physiol, January 1, 2005; 288(1): C122 - C131. [Abstract] [Full Text] [PDF]

				M. Craven, G. P. Sergeant, M. A. Hollywood, N. G. McHale, and K. D. Thornbury Modulation of spontaneous Ca2+-activated Cl- currents in the rabbit corpus cavernosum by the nitric oxide-cGMP pathway J. Physiol., April 15, 2004; 556(2): 495 - 506. [Abstract] [Full Text] [PDF]

				A. S. Piper and W. A. Large Single cGMP-activated Ca2+-dependent Cl- channels in rat mesenteric artery smooth muscle cells J. Physiol., March 1, 2004; 555(2): 397 - 408. [Abstract] [Full Text] [PDF]

				V. V. Matchkov, C. Aalkjaer, and H. Nilsson A Cyclic GMP-dependent Calcium-activated Chloride Current in Smooth-muscle Cells from Rat Mesenteric Resistance Arteries J. Gen. Physiol., January 26, 2004; 123(2): 121 - 134. [Abstract] [Full Text] [PDF]

				S. H. Kang, P. Vanden Berghe, and T. K. Smith Ca2+-activated Cl- current in cultured myenteric neurons from murine proximal colon Am J Physiol Cell Physiol, April 1, 2003; 284(4): C839 - C847. [Abstract] [Full Text] [PDF]

				G. D. S. Hirst, N. J. Bramich, N. Teramoto, H. Suzuki, and F. R. Edwards Regenerative component of slow waves in the guinea-pig gastric antrum involves a delayed increase in [Ca2+]i and Cl- channels J. Physiol., May 1, 2002; 540(3): 907 - 919. [Abstract] [Full Text] [PDF]