In humans, chronic atrial fibrillation decreases the transient outward current and ultrarapid component of the delayed rectifier current differentially on each atria and increases the slow component of the delayed rectifier current in both.

The purpose of this study was to compare the voltage-dependent K(+) currents of human cells of the right and left atria and determine whether electrical remodeling produced by chronic atrial fibrillation (CAF) is chamber-specific. Several data point to the existence of interatrial differences in the repolarizing currents. Therefore, it could be possible that CAF-induced electrical remodeling differentially affects voltage-dependent K(+) currents in each atrium. Currents were recorded using the whole-cell patch-clamp in myocytes from left (LAA) and right atrial appendages (RAA) obtained from sinus rhythm (SR) and CAF patients. In SR, LAA and RAA myocytes were divided in 3 types, according to their main voltage-dependent repolarizing K(+) current. CAF differentially modified the proportion of these 3 types of cells on each atrium. CAF reduced the Ca(2+)-independent 4-aminopyridine-sensitive component of the transient outward current (I(to1)) more markedly in the LAA than in the RAA. Therefore, an atrial right-to-left I(to1) gradient was created by CAF. In contrast, the ultrarapid component of the delayed rectifier current (I(Kur)) was more markedly reduced in the RAA than in the LAA, thus abolishing the atrial right-to-left I(Kur) gradient observed in SR. Importantly, in both atria, CAF increased the slow component of the delayed rectifier current (I(Ks)). Our results demonstrated that in SR there are intra-atrial heterogeneities in the repolarizing currents. CAF decreases I(to1) and I(Kur) differentially in each atrium and increases I(Ks) in both atria, an effect that further promotes re-entry.

Caballero R ，de la Fuente MG ，Gómez R ，Barana A ，Amorós I ，Dolz-Gaitón P ，Osuna L ，Almendral J ，Atienza F ，Fernández-Avilés F ，Pita A ，Rodríguez-Roda J ，Pinto A ，Tamargo J ，Delpón E ... -  《-》

[Differences in atrial remodelling between right and left atria in patients with chronic atrial fibrillation].

Tamargo Menéndez J 《-》

Chronic atrial fibrillation up-regulates β1-Adrenoceptors affecting repolarizing currents and action potential duration.

González de la Fuente M ，Barana A ，Gómez R ，Amorós I ，Dolz-Gaitón P ，Sacristán S ，Atienza F ，Pita A ，Pinto Á ，Fernández-Avilés F ，Caballero R ，Tamargo J ，Delpón E ... -  《-》

Demonstration of calcium-activated transient outward chloride current and delayed rectifier potassium currents in Swine atrial myocytes.

Li GR ，Sun H ，To J ，Tse HF ，Lau CP ... -  《JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY》

Alterations in outward K(+) currents on removal of external Ca(2+) in human atrial myocytes.

External divalent cations are known to play an important role in the function of voltage-gated ion channels. The purpose of this study was to examine the sensitivity of the voltage-gated K(+) currents of human atrial myocytes to external Ca(2+) ions. Myocytes were isolated by collagenase digestion of atrial appendages taken from patients undergoing coronary artery-bypass surgery. Currents were recorded from single isolated myocytes at 37 degrees C using the whole-cell patch-clamp technique. With 0.5 mM external Ca(2+), voltage pulses positive to -20 mV (holding potential = -60 mV) activated outward currents which very rapidly reached a peak (I(peak)) and subsequently inactivated (tau = 7.5 +/- 0.7 msec at +60 mV) to a sustained level, demonstrating the contribution of both rapidly inactivating transient (I(to1)) and non-inactivating sustained (I(so)) outward currents. The I(to1) component of I(peak), but not I(so), showed voltage-dependent inactivation using 100 msec prepulses (V(1/2) = -35.2 +/- 0.5 mV). The K(+) channel blocker, 4-aminopyridine (4-AP, 2 mM), inhibited I(to1) by approximately 76% and reduced I(so) by approximately 33%. Removal of external Ca(2+) had several effects: (i) I(peak) was reduced in a manner consistent with an approximately 13 mV shift to negative voltages in the voltage-dependent inactivation of I(to1). (ii) I(so) was increased over the entire voltage range and this was associated with an increase in a non-inactivating 4-AP-sensitive current. (iii) In 79% cells (11/14), a slowly inactivating component was revealed such that the time-dependent inactivation was described by a double exponential time course (tau(1) = 7.0 +/- 0.7, tau(2) = 90 +/- 21 msec at +60 mV) with no effect on the fast time constant. Removal of external Ca(2+) was associated with an additional component to the voltage-dependent inactivation of I(peak) and I(so) (V(1/2) = -20.5 +/- 1.5 mV). The slowly inactivating component was seen only in the absence of external Ca(2+) ions and was insensitive to 4-AP (2 mM). Experiments with Cs(+)-rich pipette solutions suggested that the Ca(2+)-sensitive currents were carried predominantly by K(+) ions. External Ca(2+) ions are important to voltage-gated K(+) channel function in human atrial myocytes and removal of external Ca(2+) ions affects I(to1) and 4-AP-sensitive I(so) in distinct ways.

Bertaso F ，Hendry BM ，Donohoe P ，James AF ... -  《BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS》