Reduced density and altered regulation of rat atrial L-type Ca2+ current in heart failure

Constitutive regulation by PKA has recently been shown to contribute to L-type Ca2+ current (ICaL) at the ventricular t-tubule in heart failure. Conversely, reduction in constitutive regulation by PKA has been proposed to underlie the downregulation of atrial I-CaL in heart failure. The hypothesis that downregulation of atrial I-CaL in heart failure involves reduced channel phosphorylation was examined. Anesthetized adult male Wistar rats underwent surgical coronary artery ligation (CAL, N = 10) or equivalent sham-operation (Sham, N = 12). Left atrial myocytes were isolated =18 wk postsurgery and whole cell currents recorded (holding potential =-80 mV). ICaL activated by depolarizing pulses to voltages from -40 to +50 mV were normalized to cell capacitance and current density-voltage relations plotted. CAL cell capacitances were = 1.67fold greater than Sham (P <= 0.0001). Maximal I-CaL conductance (G(max)) was downregulated more than 2-fold in CAL vs. Sham myocytes (P < 0.0001). Norepinephrine (1 = mol/l) increased G(max) > 50% more effectively in CAL than in Sham so that differences in I-CaL density were abolished. Differences between CAL and Sham G(max) were not abolished by calyculin A (100 nmol/l), suggesting that increased protein dephosphorylation did not account for ICaL downregulation. Treatment with either H-89 (10 mu mol/l) or AIP (5 mu mol/l) had no effect on basal currents in Sham or CAL myocytes, indicating that, in contrast to ventricular myocytes, neither PKA nor CaMKII regulated basal I-CaL. Expression of the L-type alpha(1C)-subunit, protein phosphatases 1 and 2A, and inhibitor-1 proteins was unchanged. In conclusion, reduction in PKA-dependent regulation did not contribute to downregulation of atrial ICaL in heart failure. NEW & NOTEWORTHY Whole cell recording of L-type Ca2+ currents in atrial myocytes from rat hearts subjected to coronary artery ligation compared with those from sham-operated controls reveals marked reduction in current density in heart failure without change in channel subunit expression and associated with altered phosphorylation independent of protein kinase A.