Biophysical and molecular comparison of sodium current in cells isolated from canine atria and pulmonary vein

The collar of the pulmonary vein (PV) is the focal point for the initiation of atrial arrhythmias, but the mechanisms underlying how PV cells differ from neighboring left atrial tissue are unclear. We examined the biophysical and molecular properties of I_Na in cells isolated from the canine pulmonary sleeve and compared the properties to left atrial tissue. PV and left atrial myocytes were isolated and patch clamp techniques were used to record I_Na. Action potential recordings from either tissue type were made using high-resistance electrodes. mRNA was determined using quantitative RT-PCR and proteins were determined by Western blot. Analysis of the action potential characteristics showed that PV tissue had a lower Vmax compared with left atrial tissue. Fast I_Na showed that current density was slightly lower in PV cells compared with LA cells (-96 ± 18.7 pA/pF vs. -120 ± 6.7 pA/pF, respectively, p < 0.05). The recovery from inactivation of I_Na in PV cells was slightly slower but no marked difference in steady-state inactivation was noted. Analysis of late I_Na during a 225-ms pulse showed that late I_Na was significantly smaller in PV cells compared to LA cells at all measured time points into the pulse. These results suggest PV cells have lower density of both peak and late I_Na. Molecular analysis of Nav1.5 and the four beta subunits showed lower levels of Nav1.5 as well as Navβ1 subunits, confirming the biophysical findings. These data show that a lower density of I_Na may lead to depression of excitability and predispose the PV collar to re-entrant circuits under pathophysiological conditions.