Ectopic foci in pulmonary veins (PV) are involved in the onset of atrial fibrillation. Norepinephrine (NE) induces in rat PV cardiomyocytes (CM) an automatic activity in saw-tooth pattern (catecholaminergic automatic activity or CAA), consisting of bursts of slow action potentials which depends on Ca (upstroke) and Na (inter burst) channels. We have previously shown the co-existence in rat PVCM, of a fast LVA (FLVA) non selective TTX-sensitive cationic channel and of T-type Ca channels.

To evaluate in male Wistar rat PV myocardial sleeve the contribution of these channels to triggering NE-induced ectopic foci.

Whole-cell currents were studied at room temperature in enzymatically isolated PVCM. Mechanical activity of PV rings was recorded in an organ bath at 37°C and CAA was induced by application of 10μM NE.

The FLVA Ca current was increased by the Cav3.x blockers TTA-A2 (10-100nM, n=11) and NiCl2 (40μM, n=9) whereas a large LVA Ca current, present in 10 out of 80 PVCM, was partially reduced by 100nM TTA-A2. Study of K currents revealed the presence of an inward rectifying current sensitive to TRAM-34 (1μM, n=6), a blocker of the Ca-activated K channel SK4. In PV rings, TTA-A2 (1-5μM) decreased CAA incidence. Total arrhythmia duration, measured over the last 10min of a 30min long drug application, was reduced as well as burst duration and the number of spontaneous twitches within a burst. On the other hand, 40μM NiCl2 or 1-2μM TRAM-34 increased total arrhythmia duration by decreasing the interval between bursts (no significant effect on the burst characteristics). Only NiCl2 had a significant negative inotropic effect (∼80% inhibition of L-type calcium current).

Our results suggest that Ca influx through Cav3.1 channels contribute to triggering bursts of automatic activity and that Cav3.2 Ca channels, through activation of SK4 channels, are involved in the regulation of the interval between bursts.