Distinctive sodium and calcium regulation associated with sex differences in atrial electrophysiology of rabbits

Background: Sex and sodium/calcium regulation play critical roles in cardiac electrophysiology and atrial arrhythmogenesis. We investigated whether sodium and calcium contributed to sex differences in atrial electrophysiology. Methods: Whole-cell patch clamp techniques and the indo-1 fluorometric ratio technique were used to investigate the ionic current and intracellular calcium in single isolated male and female rabbit myocytes from the left atrium posterior wall (LAPW) and right atrium (RA). Results: Female LAPW(n = 95) andRA(n = 49) myocytes had larger cellwidths (15.1 +/- 0.4 vs. 13.8 +/- 0.4 mu m, p < 0.05; 14.9 +/- 0.6 vs. 13.5 +/- 0.4 mu m, p < 0.05) than male LAPW(n = 142) and RA (n = 57) myocytes. Male LAPW myocytes (n = 26) had a higher incidence (57 vs. 16%, p < 0.05) of delayed after depolarizations (DADs) than female LAPW myocytes (n = 24) but there were similar incidences (20 vs. 20%, p = 0.05) of DADs in male and female RA myocytes. The late sodium current, calcium transients, and sarcoplasmic reticulum calcium contents were larger inmale than female LAPW myocytes butwere similar inmale and female RAmyocytes. However, the ICa-L and nickel-sensitive sodium/calcium exchanger currents were similar between two groups. Different from those in female myocytes, ouabain (10 mu M) only induced repeated atrial beats (0 to 45%, p < 0.05) in male myocytes (n = 11). Moreover, ranolazine (3 mu M) perfusion (4.5 +/- 0.6 vs. 1 min, p < 0.05) was required to decrease the amplitude of DADs in male but not female LAPWmyocytes. Conclusions: Increased late sodium currents and calcium contents may contribute to higher arrhythmogenesis in male LAPWmyocytes. (C) 2013 Elsevier Ireland Ltd. All rights reserved.