Diminished Ca release from the sarcoplasmic reticulum (SR) is an important contributor to the impaired contractility of the failing heart. Despite extensive effort, the underlying causes of abnormal SR Ca release in heart failure (HF) remain unknown. We used a combination of simultaneous imaging of cytosolic and SR intralu- excitation-contraction coupling ͉ ryanodine receptor ͉ sarcoplasmic reticulum

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Background and Purpose: Recent reports suggest that n‐3 (omega‐3) polyunsaturated fatty acids (PUFAs) may reduce atrial fibrillation (AF). Reduction of the atrial effective refractory period (ERP) is believed to be an important early remodeling event that favors the development and perpetuation of AF. We hypothesized that n‐3 PUFAs would attenuate early atrial electrophysiolgical remodeling in a canine model of acute atrial tachypacing. Experimental Approach: Adult dogs of either sex received n‐3 PUFAs (n=6), n‐6 PUFAs (n=6), or saline (n=6) infused over 1 h. After a stable ERP was established, treatment was initiated concurrently with 6 h of rapid atrial pacing (400 b.p.m.). Serial right atrial ERPs were measured during rapid atrial pacing, and induction of atrial tachyarrhythmias was attempted at the conclusion of each study. Key results: There was no change in P wave duration or in the PQ, QRS, QT or QTc intervals in any of the treatment groups. N‐3 PUFA treatment significantly reduced the shortening of atrial ERP, compared to both control groups (P<0.05). In separate experiments, the same n‐3 PUFA infusion was given to dogs remaining in normal sinus rhythm. During sinus rhythm, n‐3 PUFA infusion did not alter any electrocardiogram (ECG) parameter or the atrial ERP. Conclusions and Implications: We conclude that acute n‐3 PUFA treatment prevents acute atrial electrophysiological remodeling during high rate activity, which may minimize the self‐perpetuation of AF. British Journal of Pharmacology (2007) 150, 281–285. doi:

Background and purpose: I Kur (Ultra-rapid delayed rectifier current) has mM sensitivity to 4-aminopyridine (4-AP) and is an important modulator of the plateau amplitude and action potential duration in canine atria. Kv1.5 encodes I Kur and is present in both atria and ventricles in canines and humans. We hypothesized that a similar plateau outward current with mM sensitivity to 4-AP is present in canine ventricle. Experimental approach: We used established voltage clamp protocols and used 4-AP (50 and 100 mM) to measure a plateau outward current in normal canine myocytes isolated from the left ventricular mid-myocardium. Key results: Action potential recordings in the presence of 4-AP showed significant prolongation of action potential duration at 50 and 90% repolarization at 0.5 and 1 Hz (Po0.05), while no prolongation occurred at 2 Hz. Voltage clamp experiments revealed a rapidly activating current, similar to current characteristics of canine atrial I Kur , in B70% of left ventricular myocytes. The IC 50 of 4-AP for this current was 24.2 mM. The concentration of 4-AP used in our experiments resulted in selective blockade of an outward current that was not I to or I Kr . b-Adrenergic stimulation with isoprenaline significantly increased the 4-AP sensitive outward current density (Po0.05), suggesting a role for this current during increased sympathetic stimulation. In silico incorporation into a canine ventricular cell model revealed selective AP prolongation after current blockade. Conclusions and implications: Our results support the existence of a canine ventricular plateau outward current sensitive to micromolar 4-AP and its constitutive role in ventricular repolarization.

Background: Cardiomyocytes have small potential for renovation and proliferation in vivo. Consequently, the heart muscle has limited capacity of self-renewal. Mesenchymal stem cells (MSC) therapy, as well as MSC differentiated into cardiomyocytes, has been used in the attempt to minimize the effects of ischemic-hypoxic lesions and those affecting the electrical conduction system of the heart.