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This Article Full Text Full Text (PDF) All Versions of this Article: 92/3/549    most recent expphysiol.2007.037069v1 Alert me when this article is cited Alert me if a correction is posted 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 Google Scholar Google Scholar Articles by Zhou, S.-S. Articles by Li, D.-L. Search for Related Content PubMed PubMed Citation Articles by Zhou, S.-S. Articles by Li, D.-L.

¹ Institute of Basic Medical Sciences, Medical College, Dalian University, Dalian 116622, China ² Department of Physiology, Xinxiang Medical College, Xinxiang 453003, China

The effects of monocarboxylic acid-derived Cl^– channel blockers on cardiac depolarization-activated K⁺ currents were investigated. Membrane currents in rat ventricular myocytes were recorded using the whole-cell configuration of the patch-clamp technique. 5-Nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) and niflumic acid (NFA) induced an outward current at 0 mV. Both NPPB and NFA failed to induce any current when used intracellularly or after K⁺ in the bath and pipette solutions was replaced by equimolar Cs⁺. Voltage pulse protocols revealed that NPPB and NFA enhanced the steady-state K⁺ current but inhibited the transient outward K⁺ current. Genistein, a tyrosine kinase (PTK) inhibitor, inhibited NPPB- and NFA-induced outward current. Another PTK inhibitor, lavendustin A, produced a comparable effect. In contrast, the inactive analogue of genistein, daidzein, was ineffective. Orthovanadate, a tyrosine phosphatase inhibitor, markedly slowed the deactivation of the outward current induced by NPPB and NFA. The protein kinase A (PKA) inhibitor H-89 inhibited NPPB-induced outward current at 0 mV. In contrast, the protein kinase C (PKC) inhibitor H-7 was without significant effect on the action of NPPB. Pretreatment of the myocytes with genistein or H-89 prevented the enhancing effect of NPPB. Increasing intracellular Cl^– from 22 to 132 mM slightly reduced NPPB-induced outward current at 0 mV. These results demonstrate that the monocarboxylic acid-derived Cl^– channel blockers NPPB and NFA enhance cardiac steady-state K⁺ current, and suggest that the enhancing effect of the Cl^– channel blockers is mediated by stimulation of PKA and PTK signalling pathways.

(Received 15 January 2007; accepted after revision 12 February 2007; first published online 15 February 2007)
Corresponding author S-S. Zhou: Institute of Basic Medical Sciences, Medical College, Dalian University, Dalian 116622, China. Email: zhouss{at}dlu.edu.cn