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

Abstract

AT-1 cells, derived from atrial tumors in transgenic mice, have many features similar to cardiac myocytes. However, their sodium current (INa) has not been evaluated on detail. In this study, two INa phenotypes were identified in AT-1 cells: one at 3 days in culture and the other at 14 days. INa was smaller at 3 days than at 14 days (12 +/- 2 vs. 37 +/- 5 pA/pF) and activated more slowly (time to peak INa 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 3-day cells did not alter INa 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, INa 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 INa amplitude or gating.

Ionic Mechanisms of Pacemaker Activity in Spontaneously Contracting Atrial HL-1 Cells

“…Studies were also conducted to investigate I Na and its pharmacologic properties, which have not been previously explored in atrial HL-1 cells. Our results demonstrated characteristic cardiac Na + currents and current-voltage (IV) relationship (Figure 5A and 5B), as well as sensitivity to block by tetrodotoxin (TTX) similar to that observed for AT-1 cells24 (Figure 5C). …”

Identification of a T-Type Ca 2+ Channel Isoform in Murine Atrial Myocytes (AT-1 Cells)

“…10 As in developing heart, the AT-1 Na ϩ current increases progressively with time in culture. 11 AT-1 cell repolarization currents are similar to normal atrial myocytes. 10 The ultrastructure of AT-1 cells is also similar to normal atrial myocytes, including the presence of myofibrils and large secretory granules.…”

Unmasking of Brugada Syndrome by Lithium

“…19 Glass microelectrode resistance ranged from 1.0 to 1.5 M⍀. Data acquisition was performed with an Axopatch 200A patch-clamp amplifier and pCLAMP 7.0 software (Axon Instruments Inc).…”