Atrial L-Type Ca ²⁺ Currents and Human Atrial Fibrillation

Abstract

Chronic atrial fibrillation (AF) is characterized by decreased atrial contractility, shortened action potential duration, and decreased accommodation of action potential duration to changes in activation rate. Studies on experimental animal models of AF implicate a reduction in L-type Ca2+ current (I(Ca)) density in these changes. To evaluate the effect of AF on human I(Ca), we compared I(Ca) in atrial myocytes isolated from 42 patients in normal sinus rhythm at the time of cardiac surgery with that of 11 chronic AF patients. I(Ca) was significantly reduced in the myocytes of patients with chronic AF (mean -3.35+/-0.5 pA/pF versus -9.13+/-1. 0 pA/pF in the controls), with no difference between groups in the voltage dependence of activation or steady-state inactivation. Although I(Ca) was lower in myocytes from the chronic AF patients, their response to maximal beta-adrenergic stimulation was not impaired. Postoperative AF frequently follows cardiac surgery. Half of the patients in the control group (19/38) of this study experienced postoperative AF. Whereas chronic AF is characterized by reduced atrial I(Ca), the patients with the greatest I(Ca) had an increased incidence of postoperative AF, independent of patient age or diagnosis. This observation is consistent with the concept that calcium overload may be an important factor in the initiation of AF. The reduction in functional I(Ca) density in myocytes from the atria of chronic AF patients may thus be an adaptive response to the arrhythmia-induced calcium overload.

Dynamics of human atrial cell models: Restitution, memory, and intracellular calcium dynamics in single cells

“…The reduction in rate adaptation shown by the models is in agreement with a number of experimental studies that show little rate adaptation in MAP recordings shortly after cardioversion of chronic AF (Franz et al, 1997;Kamalvand et al, 1999;Manios et al, 2000;Osaka et al, 2000) and in isolated myocytes (Bosch et al, 1999;Van Wagoner et al, 1999;Workman et al, 2001) and tissues (Boutjdir et al, 1986) obtained from right atrial appendage tissue of patients with chronic AF. In some cases, more significant rate adaptation can be observed at the shortest CLs (Kim et al, 2002;Dobrev and Ravens, 2003).…”

“…In some cases, more significant rate adaptation can be observed at the shortest CLs (Kim et al, 2002;Dobrev and Ravens, 2003). Similar alterations to those given by Courtemanche et al (1999) have been observed in other experiments as well (Dobrev and Ravens, 2003), including substantial reductions in I Ca,L (Bosch et al, 1999;Van Wagoner et al, 1999;Skasa et al, 2001;Workman et al, 2001) and I to (Van Wagoner et al, 1997;Bosch et al, 1999;Brandt et al, 2000;Grammer et al, 2000;Workman et al, 2001). The reduction in I Kur proposed by Courtemanche et al (1999) has been found in some studies (Van Wagoner et al, 1997;Brandt et al, 2000) but not in others (Grammer et al, 2000;Workman et al, 2001).…”

Arrhythmias, elicited by catecholamines and serotonin, vanish in human chronic atrial fibrillation

“…In patients with AF, the difference between reduced 5-HT signals and catecholamine signals became more pronounced (Figs. 4 and 5), possibly related to the well-known increase in atrial myocyte size in AF (3,4). This would increase the diffusion path and dissipation of cAMP from its formation by the cell membrane-bound AC to its intracellular effectors.…”

“…Atrial contractility is reduced in isolated atrial tissues (3) obtained from patients with chronic AF, attributed to a marked decrease in L-type Ca 2+ current (I Ca,L ) (3,4). The inotropic responses to the agonist for β 1 -adrenergic receptors (β 1 ARs) and β 2 -adrenergic receptors (β 2 ARs), isoproterenol (ISO), but not the density of βARs and G proteins, are decreased in AF (3); however, whether the function of coexisting β 1 ARs and/or β 2 ARs is perturbed is unknown.…”

Estresse crônico melhora a função miocárdica sem alterar a atividade do canal-L para Ca+2 em ratos

“…in density or role of the L-type calcium channel have been implicated in a variety of cardiovascular diseases 16,17 . Given this information, the objective was to test the hypothesis that chronic stress promotes cardiac dysfunction associated to L-type calcium Ca 2+ channel activity depression.…”