Regulation of sodium current development in cultured atrial tumor
myocytes (at-1 cells).
Yang, Tao, and Dan M. Roden.
Departments of Pharmacology and Medicine, Vanderbilt University,
Nashville, Tennessee 37232
APStracts 3:0024H, 1996.
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 in 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 msec). Inactivation at 14 days was
faster and shifted 16 mV negative compared to 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 cAMP analog CPT-cAMP, the phorbol ester PMA or okadaic acid
was added to the culture medium from days 0 to 3. Conversely, the
protein kinase A inhibitor Rp-cAMPS 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 which 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.
Received 16 August 1995; accepted in final form 20 December 1995.
APS Manuscript Number H776-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 January 96