No significant sex differences in Iso-induced decrease of CaD₈₀.

<p>A) Representative CaTs at baseline (<i>green traces</i>) and during treatment with Iso (316.2 nM, <i>orange traces</i>) normalized and superimposed to demonstrate the Iso-induced shortening of CaD₈₀ at both 3 Hz <i>(top)</i> and 5.5 Hz <i>(bottom)</i> pacing. B) Summary data for the decrease in CaD₈₀ (versus baseline values) as a function of the dose of Iso (1, 10, 31.6, 100, 316.2 nM) in the LV base <i>(left)</i> and apex <i>(right)</i> with pacing at 3 (<i>top</i>) and 5.5 Hz (<i>bottom</i>) for female (n = 5) and male (n = 5) hearts. Female versus male, p = NS for all comparisons.</p

Optical mapping of V_m and Ca²⁺ in isolated rabbit hearts.

<p><i>Left</i>, Langendorff-perfused isolated rabbit heart mounted in the tissue bath with the anterior surface of the ventricles centered in the viewing window. <i>Center</i>, heart illuminated with the high power green (530 nm peak λ) LEDs with the black box representing the field of view. <i>Right</i>, representative recordings of the volume-conducted electrocardiogram (ECG), optical AP (V_m), and CaT (Ca²⁺) measured simultaneously during a single paced beat.</p

Baseline sex differences in steady-state ventricular APs and CaTs.

<p>Summary data for action potential duration (APD₉₀, ms), calcium transient duration (CaD₈₀, ms) and the time constant of calcium recovery (τ, ms) at 3 and 5.5 Hz pacing at either the LV base <i>(left)</i> or apex <i>(right)</i> in the absence of β-adrenergic stimulation (baseline). *p<0.05, female vs male.</p

Iso-induced SCR and ectopic activity.

<p>A) Representative CaTs from a male heart during the last three paced beats (S1) of a 3 Hz drive train. <i>Top</i>, at baseline calcium levels return to diastole. During treatment with Iso (31.6 nM), an SCR occurs shortly after the return to diastolic calcium levels. B) Sex differences in the frequency of pacing protocols that elicited SCRs and EBs during treatment with Iso. C) Simultaneous recordings of Ca²⁺, V_m, and the volume-conducted ECG from a male heart showing the last three paced beats (S1) followed by an SCR (arrow) and an EB elicited by treatment with 31.6 nM Iso. Note that the smaller, regularly occurring activations (#) in the ECG are derived from the intrinsic activity of the left atrium. This confirms the complete atrioventricular dissociation in CHB hearts. D) Sex difference in the coupling interval (ms) between the activation of the last paced beat and EBs elicited during treatment with Iso. *p<0.05, female vs male.</p

Less Iso-induced decrease of APD₉₀ in female hearts.

<p>A) Representative APs at baseline (<i>green traces</i>) and during treatment with Iso (316.2 nM, <i>orange traces</i>) normalized and superimposed to demonstrate the sex difference in Iso effects during pacing at 3 Hz (<i>top</i>) and 5.5 Hz (<i>bottom</i>). B) Summary data for the decrease in APD₉₀ (versus baseline values) as a function of the dose of Iso (1, 10, 31.6, 100, 316.2 nM) in the LV base (left) and apex of female (n = 5) and male (n = 5) hearts during pacing at 3 Hz (<i>top</i>) and 5.5 Hz (<i>bottom</i>). *p<0.05, female versus male.</p

Image_1_Intercalated Disk Extracellular Nanodomain Expansion in Patients With Atrial Fibrillation.PDF

<p>Aims: Atrial fibrillation (AF) is the most common sustained arrhythmia. Previous evidence in animal models suggests that the gap junction (GJ) adjacent nanodomain – perinexus – is a site capable of independent intercellular communication via ephaptic transmission. Perinexal expansion is associated with slowed conduction and increased ventricular arrhythmias in animal models, but has not been studied in human tissue. The purpose of this study was to characterize the perinexus in humans and determine if perinexal expansion associates with AF.</p><p>Methods: Atrial appendages from 39 patients (pts) undergoing cardiac surgery were fixed for immunofluorescence and transmission electron microscopy (TEM). Intercalated disk distribution of the cardiac sodium channel Nav1.5, its β1 subunit, and connexin43 (C×43) was determined by confocal immunofluorescence. Perinexal width (Wp) from TEM was manually segmented by two blinded observers using ImageJ software.</p><p>Results: Nav1.5, β1, and C×43 are co-adjacent within intercalated disks of human atria, consistent with perinexal protein distributions in ventricular tissue of other species. TEM revealed that the GJ adjacent intermembrane separation in an individual perinexus does not change at distances greater than 30 nm from the GJ edge. Importantly, Wp is significantly wider in patients with a history of AF than in patients with no history of AF by approximately 3 nm, and Wp correlates with age (R = 0.7, p < 0.05).</p><p>Conclusion: Human atrial myocytes have voltage-gated sodium channels in a dynamic intercellular cleft adjacent to GJs that is consistent with previous descriptions of the perinexus. Further, perinexal width is greater in patients with AF undergoing cardiac surgery than in those without.</p