Pulmonary vein (PV) cardiomyocytes play an important role in atrial fibrillation; however, little is known about their specific cellular electrophysiological properties. We applied standard microelectrode recording and whole-cell patch-clamp to evaluate action potentials and ionic currents in canine PVs and left atrium (LA) free wall. Resting membrane potential (RMP) averaged -66 +/- 1 mV in PVs and -74 +/- 1 mV in LA (P < 0.0001) and action potential amplitude averaged 76 +/- 2 mV in PVs vs. 95 +/- 2 mV in LA (P < 0.0001). PVs had smaller maximum phase 0 upstroke velocity (Vmax: 98 +/- 9 vs. 259 +/- 16 V s(-1), P < 0.0001) and action potential duration (APD): e.g. at 2 Hz, APD to 90% repolarization in PVs was 84 % of LA (P < 0.05). Na+ current density under voltage-clamp conditions was similar in PV and LA, suggesting that smaller Vmax in PVs was due to reduced RMP. Inward rectifier current density in the PV cardiomyocytes was approximately 58% that in the LA, potentially accounting for the less negative RMP in PVs. Slow and rapid delayed rectifier currents were greater in the PV (by approximately 60 and approximately 50 %, respectively), whereas transient outward K+ current and L-type Ca2+ current were significantly smaller (by approximately 25 and approximately 30%, respectively). Na(+)-Ca(2+)-exchange (NCX) current and T-type Ca2+ current were not significantly different. In conclusion, PV cardiomyocytes have a discrete distribution of transmembrane ion currents associated with specific action potential properties, with potential implications for understanding PV electrical activity in cardiac arrhythmias.

for instantaneous inward-rectifier current, P < 0.01), and showed similar Cs + sensitivity to instantaneous current. I KH was potently blocked by tertiapin-Q, a selective Kir3-subunit channelblocker(IC 50 10.0 ± 2.1 nM),wasunaffectedbyatropineandwassignificantlyincreased by isoproterenol (isoprenaline), carbachol and the non-hydrolysable guanosine triphosphate analogue GTPγS. I KH activation by carbachol required GTP in the pipette and was prevented by pertussis toxin pretreatment. Tertiapin-Q delayed repolarization in atropine-exposed multicellular atrial preparations studied with standard microelectrodes (action potential duration pre-versus post-tertiapin-Q: 190.4 ± 4.3 versus 234.2 ± 9.9 ms, PV; 202.6 ± 2.6 versus 242.7 ± 6.2 ms, LA; 2 Hz, P < 0.05 each). Seven-day atrial tachypacing significantly increased I KH (e.g. at −120 mV in PV: from −2.8 ± 0.3 to −4.5 ± 0.5 pA pF −1 , P < 0.01). We conclude that I KH is a time-dependent, hyperpolarization-activated K + current that likely involves Kir3 subunits and appears to play a significant role in atrial physiology.

Background— Congestive heart failure (CHF) downregulates atrial transient outward ( I to ), slow delayed rectifier ( I Ks ), and L-type Ca 2+ ( I Ca,L ) currents and upregulates Na + -Ca 2+ exchange current ( I NCX ) (ionic remodeling) and causes atrial fibrosis (structural remodeling). The relative importance of ionic versus structural remodeling in CHF-related atrial fibrillation (AF) is controversial. Methods and Results— We measured hemodynamic and echocardiographic parameters, mean duration of burst pacing–induced AF (DAF), and atrial-myocyte ionic currents in dogs with CHF induced by 2-week ventricular tachypacing (240 bpm), CHF dogs allowed to recover without pacing for 4 weeks (REC), and unpaced controls. Left ventricular ejection fraction averaged 58.6±1.2% (control), 36.2±2.3% (CHF, P <0.01), and 57.9±1.6% (REC), indicating full hemodynamic recovery. Similarly, left atrial pressures were 2.2±0.3 (control), 13.1±1.5 (CHF), and 2.4±0.4 (REC) mm Hg. CHF reduced I to density by ≈65% ( P <0.01), decreased I Ca,L density by ≈50% ( P <0.01), and diminished I Ks density by ≈40% ( P <0.01) while increasing I NCX density by ≈110% ( P <0.05). In REC, all ionic current densities returned to control values. DAF increased in CHF (1132±207 versus 14.3±8.8 seconds, control) and remained increased with REC (1014±252 seconds). Atrial fibrous tissue content also increased in CHF (2.1±0.2% for control versus 10.2±0.7% for CHF, P <0.01), with no recovery observed in REC (9.4±0.8%, P <0.01 versus control, P =NS versus CHF). Conclusions— With reversal of CHF, there is complete recovery of ionic remodeling, but the prolonged-AF substrate and structural remodeling remain. This suggests that structural, not ionic, remodeling is the primary contributor to AF maintenance in experimental CHF.

Greater ERG and KvLQT1 abundance in pulmonary vein cardiomyocytes, lower abundance of Kir2.3 in pulmonary veins and differential pulmonary vein subcellular distribution of Kir2.3, ERG and KvLQT1 subunits may contribute to ionic current differences between pulmonary vein and left atrial cardiomyocytes.