title: Biophysical and molecular comparison of sodium current in cells isolated from canine atria and pulmonary vein.
abstract: 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 INain 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 INa. 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 INashowed 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 INain PV cells was slightly slower but no marked difference in steady-state inactivation was noted. Analysis of late INaduring a 225-ms pulse showed that late INawas 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 INa. 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 INamay lead to depression of excitability and predispose the PV collar to re-entrant circuits under pathophysiological conditions.
authors.affiliation: Department of Experimental Cardiology, Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, NY, 13501, USA.
authors.forename: Hector
authors.initials: H
authors.lastname: Barajas-Martinez
authors.affiliation: Department of Experimental Cardiology, Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, NY, 13501, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Goodrow
authors.affiliation: Department of Experimental Cardiology, Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, NY, 13501, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of Experimental Cardiology, Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, NY, 13501, USA.
authors.forename: Payal
authors.initials: P
authors.lastname: Patel
authors.affiliation: Department of Experimental Cardiology, Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, NY, 13501, USA.
authors.forename: Mayurika
authors.initials: M
authors.lastname: Desai
authors.affiliation: Department of Experimental Cardiology, Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, NY, 13501, USA.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Panama
authors.affiliation: Department of Experimental Cardiology, Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, NY, 13501, USA.
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Treat
authors.affiliation: Department of Experimental Cardiology, Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, NY, 13501, USA.
authors.forename: Gary L
authors.initials: GL
authors.lastname: Aistrup
authors.affiliation: Department of Experimental Cardiology, Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, NY, 13501, USA. jcordeiro@mmrl.edu.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Cordeiro
mesh_terms: D000200:Action Potentials; D000818:Animals; D002478:Cells, Cultured; D004285:Dogs; D005260:Female; D006325:Heart Atria / Q000166:cytology*; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000502:physiology*; D011667:Pulmonary Veins / Q000166:cytology*; D012964:Sodium / Q000378:metabolism; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism*
chemical_list: D061566:Voltage-Gated Sodium Channels; D012964:Sodium
keywords: Action potentials; Atria; Patch clamp; Pulmonary vein; Sodium current