title: 2-APB induces instability in rat left atrial mechanical activity.
abstract: Atrial contractile abnormalities are common clinical disorders but few pharmacological models can reliably produce such abnormalities in isolated atrial muscle. Since sarcoplasmic reticulum (SR) calcium leak may underlie these contractile irregularities, we investigated whether 2-aminoethoxydiphenyl borate (2-APB), a calcium leak-inducer, affects mechanical function in isolated, superfused rat left atria. Exposing left atria paced at 3 Hz to >10 microM 2-APB produced sporadic mechanical events that occurred in the absence of pacing stimulus. Prolonging atrial diastole in the presence of 2-APB produced spontaneous mechanical activity (SMA) defined as numerous mechanical events occurring in the absence of pacing stimulus. SMA depends on atrial sodium and chloride gradients as decreasing superfusate concentration of either ion suppressed SMA. Increasing superfusate potassium to produce an EK of approximately -74mV reversed SMA, revealing possible membrane potential sensitivity. Mechanical function decreased with time in left atria treated with 2-APB and low sodium or the anion transport inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) compared with atria exposed to low sodium or DIDS alone, suggesting 2-APB may decrease left atrial SR activator calcium. Thus, 2-APB produces instability in regular left atrial mechanical activity that may require forward-mode sodium-calcium exchange and chloride channel activities. This data identify a new model for studying atrial contractile abnormalities.
authors.affiliation: Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. wolk@uab.edu
authors.forename: Paul E
authors.initials: PE
authors.lastname: Wolkowicz
authors.forename: Hsien Chin
authors.initials: HC
authors.lastname: Wu
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Urthaler
authors.forename: David D
authors.initials: DD
authors.lastname: Ku
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D016279:Atrial Function, Left / Q000187:drug effects*; D001896:Boron Compounds / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002304:Cardiac Pacing, Artificial; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism; D003971:Diastole / Q000187:drug effects; D004195:Disease Models, Animal; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009994:Osmolar Concentration; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012107:Research Design; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000187:drug effects / Q000378:metabolism
chemical_list: D001896:Boron Compounds; D018118:Chloride Channels; D015221:Potassium Channels; D015222:Sodium Channels; D019831:Sodium-Calcium Exchanger; D012964:Sodium; C109986:2-aminoethoxydiphenyl borate; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D002118:Calcium