Regulation of sodium current development in cultured atrial tumor myocytes (AT-1 cells)

AT-1 cells, derived from atrial tumors in transgenic mice, have many features similar to cardiac myocytes. However, their sodium current (I-Na) has not been evaluated in detail. In this study, two I-Na phenotypes were identified in AT-1 cells: one at 3 days in culture and the other at 14 days. I-Na was Smaller at 3 days than at 14 days (12 +/- 2 vs. 37 +/- 5 pA/pF) and activated more slowly (time to peak I-Na, at -30 mV: 9.8 +/- 0.4 vs. 1.4 +/- 0.1 ms). Inactivation at 14 days was faster and shifted 16 mV negative compared with that at 3 days. Acute protein kinase A or C stimulation in S-day cells did not alter I-Na, gating. However, the 14-day phenotype was observed in 3-day cells when the adenosine 3',5'-cyclic monophosphate analogue 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate, the phorbol ester phorbol 12-myristate 13-acetate, or okadaic acid was added to the culture medium from days 0 to 3. Conversely, adenosine 3',5'-cyclic monophosphothioate triethylamine, the protein kinase A inhibitor. prevented the normal development of the 14-day phenotype if the exposure was early and reverted the phenotype to that at 3 days if the exposure was later. Thus, in AT-1 cells, as in other mammalian cardiac myocytes, I-Na undergoes a maturation process that is dependent on intracellular phosphorylation processes. The data raise the possibility that an important consequence of altered intracellular signaling in disease is lability in I-Na amplitude or gating.