title: Anion channels influence ECC by modulating L-type Ca(2+) channel in ventricular myocytes.
abstract: Anion channels are extensively expressed in the heart, but their roles in cardiac excitation-contraction coupling (ECC) are poorly understood. We, therefore, investigated the effects of anion channels on cardiac ventricular ECC. Edge detection, fura 2 fluorescence measurements, and whole cell patch-clamp techniques were used to measure cell shortening, the intracellular Ca(2+) transient, and the L-type Ca(2+) current (I(Ca,L)) in single rat ventricular myocytes. The anion channel blockers 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) and niflumic acid reversibly inhibited the Ca(2+) transients and cell shortening in a dose-dependent manner. Comparable results were observed when the majority of the extracellular Cl(-) was replaced with the relatively impermeant anions glutamate (Glt(-)) and aspartate (Asp(-)). NPPB and niflumic acid or the Cl(-) substitutes did not affect the resting intracellular Ca(2+) concentration but significantly inhibited I(Ca,L). In contrast, replacement of extracellular Cl(-) with the permeant anions NO, SCN(-), and Br(-) supported the ECC and I(Ca,L), which were still sensitive to blockade by NPPB. Exposure of cardiac ventricular myocytes to a hypotonic bath solution enhanced the amplitude of cell shortening and supported I(Ca,L), whereas hypertonic stress depressed the contraction and I(Ca,L). Moreover, cardiac contraction was completely abolished by NPPB (50 microM) under hypotonic conditions. It is concluded that a swelling-activated anion channel may be involved in the regulation of cardiac ECC through modulating L-type Ca(2+) channel activity.
authors.affiliation: Department of Physiology, The Fourth Military Medical University, Xi'an 710032, China. sszhou@fmmu.cn
authors.forename: Shi-Sheng
authors.initials: SS
authors.lastname: Zhou
authors.forename: Zhan
authors.initials: Z
authors.lastname: Gao
authors.forename: Ling
authors.initials: L
authors.lastname: Dong
authors.forename: Yan-Feng
authors.initials: YF
authors.lastname: Ding
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Zhang
authors.forename: Yue-Min
authors.initials: YM
authors.lastname: Wang
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Pei
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Xin-Liang
authors.initials: XL
authors.lastname: Ma
mesh_terms: D000818:Animals; D000838:Anions / Q000378:metabolism*; D001224:Aspartic Acid / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000502:physiology*; D002712:Chlorides / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000494:pharmacology; D006352:Heart Ventricles; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009544:Niflumic Acid / Q000494:pharmacology; D009579:Nitrobenzoates / Q000494:pharmacology; D009997:Osmotic Pressure; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000838:Anions; D020746:Calcium Channels, L-Type; D002712:Chlorides; D007473:Ion Channels; D009579:Nitrobenzoates; D001224:Aspartic Acid; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D018698:Glutamic Acid; D009544:Niflumic Acid; D002118:Calcium