Abstract
Ectopic activity arising from cardiomyocytes (CM) in the pulmonary vein (PV) plays a prominent role in the onset of atrial fibrillation in humans. Norepinephrine induces an automatic activity occurring in bursts in rat PV CM (but not in left atria; LA) which depends on Ca channels. Thus, the aim of this study was to compare the Ca current I Ca in rat PV and LA CM (and for comparison, left ventricle – LV) from adult male Wistar rats. Whole cell I Ca (2mM CaCl 2 ) was recorded with classical Na + - and K + -free solutions. Peak I Ca density at +15mV is significantly higher in PV (4.64±0.20pA/pF, n=56) than in LA CM (3.44±0.19pA/pF, n=25, P<0.01) and identical to that of LV CM (5.00±0.39 pA/pF, n=25). The IV curve is biphasic in PV and LA CM due to an I Ca T-like current present between -55 and -30mV representing respectively 10% and 5% of maximum peak I Ca . Although it is insensitive to nifedipine (NIF, 5 and 10μM), increased by CaCl 2 (2 to 5mM) and suppressed by its removal, the lack of effect of NiCl 2 (40μM) and of TTA-A2 (10 and 100nM) suggest that Ca v 3.1 and Ca v 3.2 expressed in the rat heart are not involved in this fast activating and inactivating current. Moreover, its blockade by 10μM TTX and its mid inactivation potential of –85 mV strongly suggest that this I Ca TTX is due to Ca permeation through Na channels. A second TTX-insensitive low threshold activated I Ca with slower kinetics is also present (half inactivation at –65mV). NIF (5μM) inhibited the major high-threshold I Ca component activating at ~-30mV with the sequence LV (-80.0±5.0%, n=6) > LA (–71.0±5.6%, n=5) ≥ PV (-63.4±3.05%, n=9) and NiCl 2 (40μM) with PV (–78.6±4.8%, n=9) > LA (-69.9±4.2%, n=6) > LV (-62.2±3.9%, n=6), suggesting that part of the current flows through Ca v 3.2 channels. However, TTAA2 (10nM) was found not so specific of Ca v 3.x as it partially inhibited I Ca in both PV and LV CM and decreased NIF efficacy. In conclusion, at least three components of Ca current are present in rat PV and LA CM. The author hereby declares no conflict of interest
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